Luigi and Mario are relaxing in their mansion. Mario sees something in the newspaper, which reveals that a rich woman from a nearby kingdom (probably Sarasaland or the Freezeen Kingdom) was killed when her mansion collapsed on her. Later, Luigi goes out for some errands, and when he gets back, his mansion is once again haunted. He runs to E. Gadd's lab to ask him about it, but E. Gadd is missing. He finds a note which reads "Beware of Cash". Luigi is confused, but finds the Poltergust 3000 hidden in the closet- however, the other Poltergusts are missing. He quickly arms himself and attempts to enter the mansion. However, the ground collapses under him and he finds himself in the basement. To save his friends, Luigi must get to the roof.
Playable Characters work like they do in SM64DS. After rescuing the character, you can enter a certain door in the mansion to change to them.
- Luigi - Luigi is the main hero of the game. He uses his Poltergust 3000 to defeat Boos.
- Mario - Mario is Luigi's brother. He uses his FLUDD to squirt water.
- E. Gadd - E. Gadd is the eldery scientist. He uses his Torcher Device to blow fire.
- Toad - Toad is the short Mushroom. He uses his ICED to blow ice.
There are two main villains, as well as 13 other Portrait Ghosts, all of which will be listed here.
- Mei - Mei is the first Portrait ghost. She is found in the Cellar, the first room in the game.
- Entardo - Entardo is the second Portrait ghost. He is found in the Pipe Room and uses fire attacks.
- Wallace - Wallace is the third Portrait ghost, and the boss of the basement. He is found in the Secret Altar.
- Shigeru - Shigeru is the fourth Portrait ghost, and the first in the main floor. He is found in the Storage Room.
- Teena - Teena is the fifth Portrait ghost. She is found in the Wardrobe Room and somehow can shrink.
- Sir Exton