In the metropolis of Champion City, the would-be superhero team of Mr. Furious (Ben Stiller), the Shoveler (William H. Macy), and the Blue Raja (Hank Azaria) attempt to make a name for themselves, but their suspect skills make them ineffective, and they find themselves upstaged by the city's most successful superhero, Captain Amazing (Greg Kinnear). However, Amazing is finding that his effectiveness at fighting crime has practically made his job obsolete, and without any worthy adversaries remaining (some of them are either dead, in exile, or still in jail), his corporate sponsors are beginning to pull their funding. To create a need for himself, Amazing uses his alter ego, billionaire lawyer Lance Hunt, to argue for the release of insane supervillain Casanova Frankenstein (Geoffrey Rush). The plan backfires; once reunited with Tony P (Eddie Izzard) and his Disco Boys, Casanova Frankenstein blows up the insane asylum, captures Amazing, and prepares to unleash a doomsday device: the "Psycho-frakulator", which lethally bends reality. Mr. Furious, while spying on Casanova Frankenstein's mansion, discovers Amazing's capture and informs the others.
After an unsuccessful rescue attempt, the three realize they need more allies, and through word-of-mouth and try-outs, they recruit Invisible Boy (Kel Mitchell), the Spleen (Paul Reubens), and the Bowler (Janeane Garofalo). The newly formed team "assaults" Casanova, which only succeeds in annoying him and damaging his car. While drunk from celebrating their victory, the team is nearly killed in retaliation by Tony P and the Disco Boys, but they are saved at the last minute by the Sphinx (Wes Studi). The Sphinx trains them, but his methods annoy Mr. Furious   he has them complete rote team-building exercises and speaks exclusively in Chiasmus. They also seek out mad scientist Doc Heller (Tom Waits), who specializes in non-lethal weaponry, to equip them for their battle.
The group breaks into Casanova's mansion during a gathering of several of the city's gangs; but, while attempting to free Captain Amazing, they inadvertently set off the Psycho-frakulator, killing him instead. Without Amazing, the team despairs of saving the city, but the Shoveler delivers a pep-talk that succeeds in uniting and inspiring them.
With new-found purpose, they assault the mansion and, by making effective use of their negligible superpowers and Heller's weapons, manage to subdue most of Casanova Frankenstein's henchmen. Unfortunately, as the heroes approach Casanova Frankenstein, he reveals that he is holding Mr. Furious' girlfriend Monica (Claire Forlani) hostage, and proceeds to activate the Psycho-frakulator, which begins to wreak havoc upon the city. While the team tries to stop the device, Mr. Furious takes on Casanova Frankenstein. After initially taking a beating, Mr. Furious unleashes his inner rage and manages to fight effectively for the first time. He defeats Casanova Frankenstein, who is thrown into the core of the Psycho-frakulator and killed by its reality-bending powers. The rest of the team helps The Bowler use her bowling ball to destroy the device and escape the mansion as it implodes.
The team is interviewed by reporters, begging to know their team name. As they argue among themselves, one reporter states "Well, whatever you may call them, Champion City will forever owe a debt of gratitude to these 'Mystery Men'," but the others are too busy arguing to hear it.
Output: Who trains the group to prepare for Casanova and his team?