MNM was called up to WWE's SmackDown! roster in April 2005. They made their debut during Carlito's interview segment, Carlito's Cabana, where they interrupted an interview between Carlito and Rey Mysterio, attacking Mysterio, and beginning a feud with Mysterio and his partner, Eddie Guerrero, over the WWE Tag Team Championship. Two weeks later, in their debut match on the SmackDown! brand, they defeated Mysterio and Guerrero to win the WWE Tag Team titles after Guerrero walked out in the middle of the match. While Nitro and Mercury held the championship, Melina was placed in an angle with Heidenreich. She publicly mocked him and was the impetus for an attack on him by Nitro and Mercury. During the assault, Road Warrior Animal saved Heidenreich from the attack. Together, Heidenreich and Road Warrior Animal, challenged Mercury and Nitro for the tag titles at the Great American Bash, in which they defeated MNM to win the titles.
The loss of the tag team championship was seen as "bad publicity" by Melina so she introduced Jillian Hall, a storyline spin doctor to repair their image. Hall got them a cover article in SmackDown! magazine. In September 2005, Hall left the group to join John "Bradshaw" Layfield (JBL), who had lost a match to Rey Mysterio.
On the October 28, 2005, episode of SmackDown!, Mercury and Nitro were placed into a tag team title fatal four way match alongside the teams of the Mexicools (Super Crazy and Psicosis), William Regal and Paul Burchall, and the WWE Tag Team Champions Legion of Doom 2005 (Heidenreich and Road Warrior Animal). During the match, Mercury and Nitro were able to perform the Snapshot on Heidenreich, to win the title for a second time. On the December 6, 2005, episode of SmackDown!, a tag team title match was scheduled between MNM and the team of Batista and Rey Mysterio. In this same episode, Melina was placed in an angle with her trying 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 acts, 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 title. 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 title. Henry was only with the group a short time before his contract was, in storyline, sold to Daivari.
In April 2006, MNM were placed in an angle in which they found themselves in a losing streak against the team of Paul London and Brian Kendrick. In non-title tag team matches, singles matches, and even a six-man tag match, London and Kendrick defeated the duo every time. At the Judgment Day pay-per-view in May 2006, in a title match, MNM lost the titles to London and Kendrick. After the match, Nitro and Mercury started brawling, disbanding the group. Later that night, Melina lost a singles match against Jillian Hall and after slapping General Manager Theodore Long in anger, she and Nitro were kayfabe fired from the SmackDown! brand.
MNM reunited in late November 2006 to answer an open challenge put out by The Hardys (Matt and Jeff) for the December to Dismember pay-per-view. At the event, MNM lost to the Hardys. MNM and the Hardys met again at Armageddon as part of a fatal four way ladder match, which also included the teams of Dave Taylor and William Regal and Paul London and Brian Kendrick. During the match, which saw London and Kendrick retain, Mercury was legitimately injured when he was struck in the face with a ladder, necessitating a trip to the emergency room where his broken nose received 15 stitches. The facial injury was worked into the angle, and when Mercury returned wearing a protective covering on his face, the rivalry between the teams intensified with MNM actively seeking to injure one or both of the Hardys, even going so far as to attack and perform a Snapshot on Matt on exposed concrete following a match.
After their feud with the Hardys was over, Nitro and Melina continued to team on Raw, while Mercury wrestled in singles competition on SmackDown!, mostly being used to win matches. On March 26, 2007, through WWE's official website, it was announced that Mercury had been released from his contract, thus ending MNM as a stable. Melina and Nitro's association began to fizzle out when Melina became the WWE Women's Champion and began garnering attention as a singles performer. During the 2007 supplemental draft, Nitro moved to the ECW brand and renamed his ring name to John Morrison, while Melina remained on Raw.