On June 11, 2016, Nese was announced as a participant for WWE's Cruiserweight Classic tournament. The tournament began on June 23, with Nese defeating Anthony Bennett in his first round match. On July 14, Nese was eliminated from the tournament by Brian Kendrick. On the September 26 episode of Raw, Nese made his main roster debut, losing to Cruiserweight Champion T.J. Perkins. On the October 3 episode of Raw, Nese won his first match on the main roster against Rich Swann. Nese made his pay-per-view debut on the Hell in a Cell pre-show, teaming with Drew Gulak and Ariya Daivari in a losing effort to Cedric Alexander, Lince Dorado and Sin Cara. On the Survivor Series pre-show, Nese, Drew Gulak and Ariya Daivari lost to T.J. Perkins, Rich Swann, and Noam Dar. In early 2017, Nese would later wrestle on 205 Live and Main Event, trading wins and losses over Gran Metalik, Lince Dorado and Mustafa Ali. Nese began aligning with Enzo Amore's faction, which, consisting of Ariya Daivari, Drew Gulak and Noam Dar, they dubbed "The Zo Train". On the December 12 episode of 205 Live, Nese was attacked by The Zo Train. Nese returned two weeks later, unsure of his position as a member of the Zo Train, and defeated Akira Tozawa. Amore was fired from WWE in January 2018, thus quietly disbanding The Zo Train.
On the February 13, 2018 episode of 205 Live, Nese was entered into a Cruiserweight Championship tournament to determine a new Cruiserweight Champion, where he was defeated by Drew Gulak in a first round. On the March 27 episode of 205 Live, Nese was defeated by Mark Andrews. On the April 10 episode of 205 Live, Nese saved Andrews from an attack of Drew Gulak, appearing to turn face in the process. On April 27, Nese participated in the Greatest Royal Rumble, entering at number 10, eliminating Hornswoggle, before being eliminated by Kofi Kingston and Xavier Woods.
Some weeks later, he aligned himself with Buddy Murphy, cementing himself as a heel again. They went on to feud with Lucha House Party (Kalisto, Gran Metalik and Lince Dorado), with the two sides trading victories. On the October 10 episode of 205 Live, Nese defeated Cedric Alexander, who had recently lost the Cruiserweight Championship to Murphy. On the October 17 episode of 205 Live, Nese won a fatal five-way match including Alexander, Gran Metalik, TJP and Lio Rush. On the October 31 episode of 205 Live, Nese lost to Mustafa Ali in a number one contender's match for the Cruiserweight Championship. Nese then began feuding with Noam Dar. On the January 29, 2019 episode of 205 Live, he was suspended indefinitely for attacking Dar in the parking lot. Nese returned on the February 12 episode of 205 Live, defeating Dar in a well-received No Disqualification match, ending their feud.
Prior to WrestleMania 35, a tournament to determine the number one contender for the Cruiserweight Championship was arranged, in which Nese defeated Kalisto in the first round, Drew Gulak in the semifinals, and Cedric Alexander in the finals to become the number one contender for the Cruiserweight Championship against his ally Buddy Murphy. After the match, he was attacked by Murphy, turning face in the process. On April 7, during the pre-show of WrestleMania 35, Nese defeated Murphy to win the Cruiserweight Championship for the first time. Two days later, on the April 9 episode of 205 Live, Nese defeated Murphy to retain his championship. At Money in the Bank, Nese defeated Ariya Daivari to retain the Cruiserweight Championship. On June 23 at Stomping Grounds, Nese lost the title to Drew Gulak in a triple threat match which also involved Akira Tozawa, ending his reign at 77 days. He would go on to lose a subsequent rematch against Gulak at Extreme Rules.
On the September 3 episode of 205 Live, he would lose to Mike Kanellis. After the match, during a backstage segment, he took out his frustrations on Oney Lorcan. Then, after the match between Humberto Carrillo and Lince Dorado, both he and Gulak would attack Carrillo and Dorado thus cementing his heel turn. On the September 17 episode of 205 Live, Nese would defeat Lorcan with Gulak's help. During the 2019 WWE Draft, Gulak was drafted to SmackDown while Nese stayed on 205 Live, thus ending their alliance. On the October 18 episode of 205 Live, Nese would defeat Oney Lorcan and Ariya Daivari in a triple threat match. On the November 6 episode of NXT, Nese was defeated by Angel Garza in a #1 contendership match for the Cruiserweight Championship. Nese returned to Raw on the December 12 episode, losing to Aleister Black and two weeks later he was defeated by Ricochet.
In April 2020, Nese was announced as a participant in the Interim Cruiserweight Title tournament representing Group A in the tournament. Nese was defeated by Kushida, Drake Maverick and Jake Atlas, failing to score a single win in the tournament. Nese would then begin feuding with Isaiah Scott, who made fun of him for not scoring a single win in the tournament, which led to them facing off on the June 3 episode of NXT and again on the June 26 episode of 205 Live, where Nese lost. On the July 3 episode of 205 Live, Nese assisted Scott in defeating Ever-Rise in a tag team match and shook hands with him after, thus turning face in the process. In late 2020, Nese aligned himself with Ariya Daivari and referred to themselves as the "205 Live OG's" and throughout the first half of 2021 would feud with newcomers such as August Grey, Curt Stallion, and Ikemen Jiro. On June 25, 2021, Nese was released from his WWE contract.