Melina made her first WWE appearance on November 29, 2004 on Raw, when Randy Orton was the guest general manager and hosted a Diva lingerie fashion show. She made another Raw appearance in December, participating in a limbo contest when Chris Jericho was general manager for the night.
Melina made her official debut in WWE as a heel as the manager of MNM (Johnny Nitro and Joey Mercury), on the April 14, 2005 episode of SmackDown!. The team interrupted the first ever Carlito's Cabana interview segment, where one half of the WWE Tag Team Champions, Rey Mysterio, was a guest. Melina insulted Mysterio and had Mercury and Nitro attack him, leading to MNM's in-ring debut the next week on SmackDown! in a title match. The team won the match against Mysterio and Eddie Guerrero, starting their first WWE Tag Team Title reign.
While managing the Tag Team Champions, Melina's character was developed to be more egotistical, as she declared herself "the most-dominant Diva in WWE". She made her official in-ring debut on June 30 against Michelle McCool, and had her first pay-per-view match against Torrie Wilson at The Great American Bash in a bra and panties match, winning both matches. In the same night, MNM dropped their championships to the Legion of Doom, prompting a new storyline where Melina hired Jillian Hall, a fixer, to assist them. MNM regained the titles on October 28 in a fatal four-Way tag team match. On the Eddie Guerrero Tribute Show, Melina won a Divas battle royal by eliminating the Women's Champion Trish Stratus. The next week, as a part of a new storyline, MNM kidnapped Stratus, tied her up and gagged her for Melina, who then challenged her to a match for the Women's Championship. The two fought at Survivor Series, with Melina losing to Stratus with the help of Mickie James.
During this time, MNM defended their titles against Rey Mysterio and the World Heavyweight Champion Batista. Melina was placed in a storyline where she tried to make Batista call off the match by visiting him in his locker room and attempting to seduce him. The storyline had the two engage in sexual intercourse, after which he simply thanked her for the "warm-up" before leaving to take part in the match, where he and Mysterio defeated MNM for the titles. The storyline played over to the next episode of SmackDown! when, before MNM invoked their rematch clause, Melina held a press conference in the ring where she claimed that Batista had sexually harassed her. During the tag team match, Mark Henry aided MNM in winning back the WWE Tag Team Championship. The storyline with Henry continued into the next year. On the first SmackDown! of 2006, Melina announced that Henry was her personal protection against Batista. He accompanied her and aided the other members of MNM in matches against Batista and Mysterio.
At Judgment Day on May 21, 2006, MNM lost their titles to Paul London and Brian Kendrick. After the match, Melina and Nitro, as part of the storyline, attacked Mercury, blaming him for the loss. Later that night, Melina lost a singles match against Jillian Hall, and after slapping General Manager Theodore Long in anger, she and Nitro were fired from the SmackDown! brand. Melina and Nitro debuted on Raw on May 29, with Nitro losing to WWE Champion John Cena. Melina continued to manage Nitro during his successful hunt for the WWE Intercontinental Championship, and in another storyline with Trish Stratus. The storyline turned into a tag team feud when Carlito teamed with Stratus after he saved her from the attacks of Melina and Nitro. At Saturday Night's Main Event XXXIII on July 15, Melina and Nitro lost to Carlito and Stratus in a mixed tag team match.
After Melina's arrival on Raw, Mick Foley began to mention her in promos and on his WWE.com columns,, and they soon formed an on-screen friendship. At SummerSlam, Melina was involved in Foley's "I Quit" match against Ric Flair, when Flair threatened to hit her with a barbed wire baseball bat, causing Foley to quit the match to save her. The next night on Raw, the storyline had Vince McMahon order Foley to join the Kiss My Ass club. After begging Foley not to go through with it, Foley "joined the club" to save Melina's job, only to have her suddenly turn on him by delivering a low blow and firing him at the behest of McMahon. It was also around this time that Melina added another characteristic to her gimmick: screaming loudly at ringside while managing or in tag team action, which became known as the "primal scream".
On January 29, 2007, Melina became the number one contender for the WWE Women's Championship after defeating Maria in a number one contender's match. On the February 5 episode of Raw, Melina received her title match against Mickie James, but was unsuccessful. After pinning James in a mixed tag team match, Melina was granted another title match. On the February 19 episode of Raw, as part of her first major singles push, Melina defeated James to win the WWE Women's Championship for the first time in her career. The feud between the two Divas continued and Melina later retained the title in a rematch during the first ever women's falls count anywhere match in WWE history.
In March, Melina was placed in an angle where she became jealous of SmackDown! Diva Ashley Massaro, who was receiving attention because of her appearance in Playboy. The angle had Melina claim in her blogs that no Playboy cover models were capable of fighting her. This resulted in scheduled matches against former Playboy cover girls Torrie Wilson and Candice Michelle, with both women losing to Melina. The storyline came to an end at WrestleMania 23, where Melina pinned Ashley in a Lumberjill match to retain her Women's Championship. After WrestleMania, Melina organized a photo op with the Women's Championship belt in the ring, but was interrupted by Mickie James, resulting in another storyline feud between the two Divas. On April 24, at a house show in Paris, France, Melina lost the Women's Championship in a triple threat match to James when James pinned Victoria, but on the orders of Jonathan Coachman, she was entitled to a rematch on the same night, where she pinned James by putting her hands on the ropes to regain the title and become a two-time WWE Women's Champion.
On May 7, 2007, Melina began feuding with Playboy cover girl Candice Michelle after she was defeated in a tag team match alongside Victoria against Candice Michelle and Mickie James. Melina continued to lose to Candice in various tag team matches, as well as in non-title bouts over the next few weeks. At Vengeance, Melina lost the Women's Championship to Candice, and failed to recapture the title at The Great American Bash.
In April 2008, Melina, along with then-ally Beth Phoenix, competed at WrestleMania XXIV in a tag team match, defeating Maria and Ashley. On the May 5 episode of Raw, Melina unintentionally attacked Phoenix with her boot during a lumberjill match with Mickie James. The following week, Phoenix walked out on Melina during a tag match against James and Maria, when Melina accidentally bumped Phoenix off the apron. Melina was then attacked by Phoenix during a backstage segment following the match, leading to Melina turning face for the first time in her WWE career. On the May 19 episode of Raw, Melina commentated during Beth Phoenix's match against Maria, which Phoenix won, and Melina would afterwards attack Phoenix with her boot before being attacked by Phoenix. At the One Night Stand pay-per-view, Melina competed in the first ever women's "I Quit" match against Beth Phoenix, but was unsuccessful. The next night on Raw, Melina teamed with former rival Mickie James in a tag team match against Beth Phoenix and Katie Lea in a losing effort. On June 23, 2008, Melina suffered a heel injury after falling from the turnbuckles during a tag team match with Mickie James against Natalya and Victoria.
Melina returned from injury on the November 24 episode of Raw, teaming with former rivals Mickie James and Candice Michelle to defeat Phoenix, Jillian Hall, and Katie Lea Burchill. The following week, she made her singles return by defeating Hall. Following the match, Melina stated her intentions to take the WWE Women's Championship from Beth Phoenix. On December 29, Melina won a six-woman battle royal to become the number one contender for the championship. After the match, Melina and Phoenix engaged in a confrontation over a fan of Phoenix's named Rosa Mendes, who had attacked Melina. On January 25, 2009, Melina won her third WWE Women's Championship at the Royal Rumble by defeating Phoenix. She retained her championship against Beth Phoenix on February 16 episode of Raw, and again during a dark match at No Way Out.
On the April 13, 2009 episode of Raw, Melina was drafted back to SmackDown as part of the 2009 WWE Draft, thus making the WWE Women's Championship exclusive to the brand. She began a feud with Michelle McCool, who was named as the number one contender to the title. McCool attacked Melina after her victory over Alicia Fox on the June 19 episode of SmackDown. Melina would then lose the Women's Championship to McCool at The Bash after an interference from Alicia Fox; she failed to regain the championship at Night of Champions.
On October 12, Melina was traded back to the Raw brand, and won the WWE Divas Championship from Divas Champion Jillian Hall, who had won the belt from Mickie James only a few minutes earlier. On the November 23 episode of Raw, Melina teamed up with Mickie James and Kelly Kelly to defeat Jillian Hall and LayCool (Michelle McCool and Layla). After the match, guest timekeeper The Gobbledy Gooker was revealed as Maryse by attacking Melina. The following week, Melina was pinned by Maryse in a tag team match. On the December 7 episode of Raw, Maryse defeated Gail Kim, and following the match, Maryse proceed to attack Kelly Kelly but was stopped by Melina. On December 29, at a WWE live event in Manchester, New Hampshire, Melina tore her ACL during a six-woman tag team match, and as a result she relinquished the Divas Championship on January 4.
Melina made her return on the August 2, 2010 episode of Raw, attacking WWE Divas Champion Alicia Fox after a six-woman tag team match in which she, Jillian Hall, and Tamina defeated Eve Torres, Gail Kim, and Natalya. At SummerSlam, Melina defeated Fox to capture the Divas Championship for the second time in her career. After the match, she was attacked by Michelle McCool and WWE Women's Champion Layla. On the 900th episode of Raw, after winning a match, she was challenged by either Layla or McCool to a Lumberjill match at Night of Champions, to unify the WWE Women's and WWE Divas Championships. McCool would win that match, after Layla attacked Melina during the match, to unify the championships. The unified championship would henceforth be known as the Divas Championship, with the Women's Championship title being retired.
On the December 20 episode of Raw, Melina became the number one contender to the Divas Championship and turned heel when she slapped then-champion Natalya, who had attempted to congratulate her following her victory. When the two fought for the Divas Championship on January 24, 2011 on Raw, Melina was defeated. On the August 1 episode of Raw, Melina participated in a number one contender's battle royal, which was won by Beth Phoenix. This would be her final match with WWE, as she was released later that week.
On the July 22, 2019 episode of Raw, Melina made her first appearance in eight years to attend the Raw Reunion show. She would make another appearance on January 4, 2021 on Raw Legends Night.
On January 29, 2022, Melina made a surprise return opening the Royal Rumble match with Sasha Banks. She was however eliminated by Banks in less than a minute.