On a quest to uncover the truth behind haunted locations and monsters, the members of Mystery, Inc. decide to explore a series of spooky sites across the United States. Over time, they grow tired of their cases, which often turned out to be elaborate costumes worn by humans pretending to be monsters. Daphne Blake, a member of the team, along with Fred Jones, focuses on their post-mystery career by hosting a popular television show dedicated to hunting real ghosts instead of fake ones. Meanwhile, the rest of the gang—Velma Dinkley, Shaggy Rogers, and Scooby-Doo—are approached by Fred to reunite for Daphne’s birthday celebration. Their reunion leads them on a road trip designed to scout haunted locations that could potentially be featured on Daphne’s supernatural-themed show.
Their journey takes them to New Orleans, Louisiana, where they are invited by Lena Dupree to visit her workplace at Moonscar Island, a mysterious place rumored to be haunted by the ghost of a pirate named Morgan Moonscar. Although the gang initially approaches the island with skepticism, intrigued by the legends and stories, they agree to explore it. Once there, they encounter a cast of interesting characters—Jacques, the ferryman who transports visitors to the island; Simone Lenoir, Lena’s employer living in a grand mansion situated on a pepper plantation; and Beau, Simone’s loyal gardener. As night falls, Shaggy and Scooby find themselves face to face with the ghost of Morgan Moonscar, who mysteriously turns into a zombie, while the rest of the team receives ghostly warnings to leave the island immediately.
Despite the eerie warnings, the gang decides to stay overnight, aiming to gather evidence for their show. That night, chaos erupts when Shaggy and Scooby are chased by a swarm of zombies—grotesque creatures that seem more real than just costume masks. Velma begins to suspect that Beau might be involved, sensing something suspicious about him. Meanwhile, Fred and Daphne manage to capture a zombie, leading them to believe it might be a human culprit in disguise. However, the discovery of the zombie’s head being pulled off reveals that these creatures are indeed authentic and not simply actors in costumes.
In the chaos, the gang becomes separated and in the process, Daphne accidentally causes Fred to fall into quicksand, losing vital film footage from their camera that could have provided evidence for their show. During a subsequent investigation in a cave, Shaggy and Scooby stumble upon wax voodoo dolls that resemble their friends, unknowingly controlling them until they unwittingly disturb a nest of bats, adding to the night’s terror. As the gang searches for answers, they uncover a secret passageway inside the mansion, where Lena claims the zombies dragged Simone away. Following the trail, they find a hidden chamber used for voodoo rituals, which causes Velma to confront Lena about her genuine intentions—she uncovers that Lena has been lying about the zombies and that Simone’s footprints are evidence of her innocence.
Simone and Lena are finally unmasked as werecats, a result of a curse originating from a legend tied to the island's settlers. Long ago, Lena and Simone were part of a group that worshiped a cat god, and when pirates led by Morgan Moonscar attacked, the settlers fled into the bayou, where they were eaten by alligators. However, Lena and Simone managed to escape and, in their desperation, prayed to their deity for protection, transforming into immortal werecats in the process. They successfully murdered the pirates but later realized that their own immortality had come at a heavy cost. Every harvest moon, the cursed women staged acts to lure victims, draining their life forces to sustain their eternal life. They employed Jacques, the ferryman, to help facilitate their sinister plans, promising him immortality in return. The zombies and ghostly apparitions haunting the island were the spirits of their previous victims, summoned to scare people away.
As the night progresses, Shaggy and Scooby accidentally disrupt the werecats’ draining ritual, which gives the rest of the gang a chance to escape. The werecats, realizing that the harvest moon has just passed, start to disintegrate into dust, releasing the spirits of their victims and ending the curse. In the final moments, Beau reveals himself as an undercover police officer investigating the mysterious disappearances linked to the island. Before leaving, Daphne suggests that Beau guest star on her show, perhaps to help shed more light on the island’s sinister history. Everyone departs the island early the next morning, their adventure having once again uncovered hidden truths behind what seemed to be supernatural phenomena.
