Jim Evers (whom Winnie the Pooh, Ash Ketchum, Littlefoot, Mickey Mouse, and all their friends are hanging out with) is a workaholic real estate agent who has little time for his family, wife Sara, teenager daughter Megan, and ten-year old son Michael who has arachnophobia. After missing his own wedding anniversary to seal a business deal, Jim promises his family to go on a weekend away to a nearby lake. Sara is contacted by the occupants of the Gracey Manor, located in the bayou swamps of New Orleans, and an eager Jim and Pooh and the others drags his family along to do business at the house. They meet Master Edward Gracey, his stern butler Ramsley, and other staff Emma and Ezra. Master Gracey invites the family to stay the night when a rainstorm floods the nearby river. Jim is taken to the library by Ramsley and Dr. Faciler who was sent by Bowser Koopa has other ghoulish surprises for our heroes, Jim becomes trapped in a secret passageway. Michael, Megan, and our heroes encounter a "ghost ball" which leads them to the mansion's attic where they find a portrait of a woman resembling Sara. Sara meets Master Gracey who explains that his ancestor's lover Elizabeth Henshaw seemingly committed suicide via poison, and his ancestor followed suit via hanging.
However, Jim encounters a gypsy woman named Madame Leota, whose head is encased in a crystal ball. After briefly being scared away, Jim, Pooh, Ash, Littlefoot, Mickey, the gang and his children learn that all of the mansion's residents are actually ghosts, cursed to be trapped in the mansion until Master Gracey and Elizabeth's ghosts are reunited, and Master Gracey believes that Sara is his lover reincarnated. In order to break the curse, Madame Leota sends the Evers family, minus Sara, into the mansion's cemetery and to a mausoleum to fetch a key. Jim and Megan locate the key, but awaken all of the mausoleum's undead inhabitants but escape unharmed, Michael rescuing them and overcoming his fear of spiders. Madame Leota points the family to a trunk in the attic, Jim and Mickey finding an old letter from Elizabeth to Edward with the promise of marriage, revealing that her suicide was false. Ramsley appears and reveals that he murdered Elizabeth to prevent Master Gracey from abandoning his home and heritage. To hide the truth, he traps the children in a trunk and literally throws Jim out of the mansion.
Master Gracey reveals to Sara his ghostly self, and obsessively believes she is Elizabeth. Ramsley And Facilier approaches Sara and blackmails her With Facilier's Magic Powder into marrying Master Gracey for the sake of her children. During the wedding ceremony, Ramsley poisons Sara's drink so that she will die and return as a ghost and end the curse. Madame Leota gives Jim the confidence to ram his car into the house, save his children and confront the ghosts. He gives the letter to Master Gracey, who confronts Ramsley, Facilier And Others. An enraged Ramsley and a ghoulish Facilier summons wraiths to kill the group and his friends from the other side, but a fiery demon emerges from the fireplace and drags Ramsley into the mouth of The Underworld. Ramsley seizes Jim and attempts to pull him down with him for ruining his plans, but then Master Gracey rescues Jim. Dr. Facilier leaves a note to our heroes saying that he'll be back with his villain alliance. Sara succumbs to the poison, but the ghost ball arrives and possesses her body, revealing itself to be Elizabeth's ghost. Elizabeth and Master Gracey kiss, and Sara is revived. In gratitude and seeking redemption, Master Gracey gives the Evers the deed to the house, allowing them to do what they want with it as long as they remain happy. The ghosts all depart the mansion and move on to Heaven.
The film ends with the Evers and our heroes driving off to the lake, accompanied by Madame Leota and four singing busts who end the film with their own rendition of "When the Saints Go Marching In".
- Ash Ketchum, Timon, Littlefoot, Mickey Mouse, Spongebob and his friends, Scooby-Doo and his friends, Ronald McDonald and his friends, all of the cartoon characters are heores, Dr. Facilier and all characters are villains will guest star in this film.