It's the year 2080 and Pluto Nash (EDDIE MURPHY) is an ex-con who's just gotten out of prison for smuggling and has talked nightclub owner and singer Anthony Frankowski (JAY MOHR) into changing his name to Tony Francis and dropping his Scottish crooner act in favor of performing as an Italian. When mob-figure Gino (BURT YOUNG) comes looking for the money Tony owes him, Pluto offers to buy and run the establishment to save Tony's life.
Seven years later, Club Pluto is a hopping place that Nash runs with his associate, Miguel (MIGUEL A NUNEZ, JR.), and gets protection from his vintage model, robotic bodyguard, Bruno (RANDY QUAID). Pluto's doing so well that he offers first-time moon visitor and aspiring singer Dina Lake (ROSARIO DAWSON) a job waiting tables so that she can make money and return to Earth.
On her first day of work, local thugs Morgan (JOE PANTOLIANO) and Kelp (VICTOR VARNADO) approach Pluto with an offer from the mysterious Rex Crater and his right-hand man Belcher (JAMES REBHORN) to buy his club for $10 million. When Pluto turns them down, they blow up his place and then repeatedly try to kill him. Against the protests of his concerned mother, Flura (PAM GRIER), Pluto then sets out to discover who's responsible and get his revenge.
With Dina and Bruno in tow, Pluto gets info or help from the likes of ex-cop Rowland (PETER BOYLE), body alternation specialist Dr. Mona Zimmer (ILLEANA DOUGLAS), smuggler Felix Laranga (LUIS GUZMÁN) and even video chauffeur James (JOHN CLEESE) as he makes his way across the moon and towards Crater's swanky casino resort.