Dudley Has A Horrible Premonition About His Old Friend Charlie Barkin About He's Going To Heaven And He's Going To Be Killed By Komplex And The Toad Empire When Their Next Target It's In The Bayou Swamps In Louisana, New Orleans Now Things Go Bumping In The Night For Dave Felis And The T.U.F.F.C.A.T.S When They Face The Most Dangerous Fear And The Life of Charlie Depends In A Golden Clock Medallion
Meanwhile In 1939 New Orleans, Dudley's Old Friend Charlie B. Barkin (Burt Reynolds), a mongrel dog with a con man's charm, is working with his gangster business partner, Carface Carruthers (Vic Tayback), at a casino fashioned out of a derelict oil tanker. Carface, unwilling to share the earnings, has Charlie imprisoned at the pound, but Charlie breaks out with the help of his best friend Itchy Itchiford (Dom DeLuise). To get Charlie out of the picture for good, Carface and his sidekick, Killer (Charles Nelson Reilly), plan and execute his murder by Orders of Komplex And The Toad Empire To Make A Trap To The T.U.F.F.C.A.T.S.
Charlie goes to Heaven by default, despite not having done a single nice thing in his life. Charlie cheats death by stealing his "life watch" (a glowing pocket watch) and winding it back up, allowing him to return to Earth. But now, if his watch stops, he will immediately die and go to Hell.
Back on Earth, Charlie reunites with Dave, Dudley, And The Taskforce And Itchy and plots his revenge against Carface by setting up a rival business. Carface, And The Toads keeps a little orphan girl named Anne-Marie (Judith Barsi) for her ability to communicate with animals, giving him an advantage when betting on races. Charlie "rescues" Anne-Marie, telling her that they will help the poor and he will find her a family but he exploits her gift just as his rival did, to make money from various animal competitions, something that she notices and becomes upset, since Charlie was using her in the same way that Carface did, but Charlie still convinces her in help him since he actually treats her fairly and kinder than Carface And Well-done.
Charlie steals a wallet from a respectable family, which Anne-Marie later finds. That night, Charlie has a nightmare in which he is banished to Hell and is attacked by Komplex, The Toads, a Hellhound (Frank Welker) and its minions.
Anne-Marie goes to return the wallet. Charlie finds her eating breakfast with the family who's wallet was stolen, where he discovers that the couple is planning to take Anne-Marie in. Charlie tricks Anne-Marie into leaving by pretending to be sick. After escaping an ambush with Carface and Killer, Charlie and Anne-Marie fall through the floor of an old warehouse into an underground sewer where they narrowly avoid being eaten by King Gator (Ken Page), a giant alligator who becomes their ally.
Itchy accuses Charlie of caring more for Anne-Marie than him or their business, Charlie, in frustration, proclaims he does not care for her at all. Anne-Marie overhears them, runs away, and is recaptured by Carface and the Toad Empire.
Charlie goes to Carface's casino/boat to rescue Anne-Marie, only to get captured and threatened with death. King Gator comes to their rescue, frees Charlie and eats Carface, while Komplex's hordes escape barely with their undead lives. Anne-Marie falls into the water, along with Charlie's watch. Charlie leaps into the water to save Anne-Marie and the watch, but is unable to get to both. He saves Anne-Marie and loses the watch, whereupon he dies a second time.
Anne-Marie ends up with her new family and Charlie is allowed back into Heaven, instead of Hell, since he gave his life to save his friend And All Thanks To The Efforts of Dave, Kitty, Oliver And Dudley.