In the decade of 2080, on a lunar colony called Little America, a retired smuggler named Pluto Nash (Eddie Murphy) buys a nightclub in order to fulfill a longtime wish and prevent the murder of Anthony Frankowski (Jay Mohr), the club's previous owner, by his creditors. Seven years later, "Club Pluto" has become a successful business that is frequented by many socialites. The staff consists of Pluto, a Hispanic assistant, and an anthropomorphic android robot named Bruno (Randy Quaid). Meanwhile, Anthony has become a stage performer under the name of Tony Francis, under which name he has achieved interplanetary fame despite his apparent lack of talent. His music, performance style, and costume resemble those of Frank Sinatra.Pluto is approached one night by a young woman called Dina Lake (Rosario Dawson), who has become stranded on the Moon and desires to earn money to pay for transport to Earth. She seeks help from Pluto because her father, "Nicky Sticks", was a friend of Pluto's, to whom offers her skills as a singer. Instead, Pluto gives her a job as server at his club and allows her to remain after closure. During the same night, Pluto is approached three times by messengers of a mysterious entrepreneur called Rex Crater, who wishes to buy Club Pluto and convert it into a gambling casino. When Pluto refuses, Rex Crater's minions destroy the club. Pluto, Dina, and Bruno escape. They therafter begin to investigate Rex Crater, about whom very little is known. Rowland (Peter Boyle), a friend to Pluto's mother and retired police detective, informs Pluto that Rex Crater is never seen outside of a penthouse in the city of Moon Beach. Rex is said to have been involved with a geneticist named Runa Pendankin, who specialized in cloning before her death.Pluto and Dina visit Doctor Pendankin's apprentice, Mona Zimmer (Illeana Douglas), who operates a cosmetic surgery station. To inflitrate this, they pose as a married couple attempting to revive their infatuation for one another by having their figures altered. After they have seen several examples of commonly preferred body shapes and contours, Zimmer asks for a police permit to perform the operation. Pluto bribes her to ignore this formality, and when she accepts the bribe poses as a police officer bent on interrogating her. Having been intimidated by Pluto's bluffs, Zimmer reveals that Doctor Pendankin had worked for or with a Terrestrial criminal having what appeared to be the initials "WZW" inscribed on his briefcase prior to her death.Pluto and Dina return to the hotel. They meet Pluto's mother, Flura Nash (Pam Grier). All are attacked by Rex Crater's assassins, who have tracked them to the hotel. They all narrowly escape, whereinafter Pluto steals a car to transport himself, Dina, and Bruno to an abandoned smuggler's refuge.At this hideout, Pluto mounts an Internet-based search for any Terrestrial criminal with the initials "WZW". When this yields nothing, Dina suggests that the initials are in fact "MZM", having been seen upside-down by Mona Zimmer. Pluto, on this basis, discovers a criminal called Michael Zoroaster Marucci (Alec Baldwin, in an uncredited cameo). Pluto suspects that Michael Marucci and Rex Crater are one and the same. Abruptly, he is contacted by his mother, who tells him that Rowland has been killed. Moments later, the hideout is attacked by Rex Crater's agents. A chase ensues; during Pluto's final evasive manouvere, their car is damaged and explodes, causing them to be presumed dead.They are eventually rescued and taken to Moon Beach by Felix Laranga (Luis Guzmán), a smuggler who idolizes Pluto Nash. They infiltrate Rex Crater's casino/hotel, where they contact Tony Francis after his concert. Tony attempts to help them, but they are captured by Rex Crater's agents and taken to him.Pluto accuses Rex Crater of being Michael Marucci, whereupon Rex Crater reveals himself to be a clone of Pluto, created by Doctor Pendankin to act as a public face of Michael Marucci's illegal activities, but who then killed Marucci. Rex coolly murders his agents who had failed to destroy Pluto, shocking most of the onlookers, then goes on to explain his elaborate plans to create a chain of "exclusive" gambling casinos from the ruins of other establishments including Club Pluto. At this, Pluto contemptuously destroys Rex's model of the casino and assaults him. Rex and Pluto then fight for possession of Rex's gun while the others watch, uncertain of which is Pluto and which is Rex.Pluto shoots Bruno when he gains possession of the gun, whereupon Rex's assistant Belcher (James Rebhorn) assumes that Pluto would not damage his own robot and shoots Rex. Pluto orders the robot guards to leave, then reveals his identity to Dina by speaking of her employment to him. When Belcher realizes the truth, he is struck down; Bruno then reveals that he was wearing a bulletproof shirt on Pluto's advice. Rex, who shares Pluto's memories and was therefore also wearing a bulletproof shirt, is revived attempts to garotte Pluto with a wire paperweight. He is then thrown through a window and dies falling into the casino below.The movie ends with the protagonists celebrating in the rebuilt Club Pluto. Bruno is made manager of the Club and Dina its lead singer. Felix is granted lifelong credit and Tony invited to the celebration. Pluto, his desires fulfilled, rests at ease.