The film masterfully executes a double twist. The first twist subverts the franchise formula: the zombies are real, physical walking corpses. However, the second, more crucial twist subverts the horror tropes: the terrifying zombies are actually the "good guys". They are the reanimated corpses of previous victims trying to warn the gang to leave the island.
The true villains are revealed to be the charming hosts, Simone Lenoir, Lena Dupree, and the ferryman Jacques. They are immortal werecats who must drain the life force of victims every harvest moon to sustain their immortality. In the climax, Shaggy and Scooby accidentally disrupt the voodoo draining ritual. The gang stalls the villains until the harvest moon passes its peak, causing the curse to backfire and reducing the werecats to dust, thereby allowing the tormented souls of the zombies to finally rest in peace.