In the beginning of the movie, Mystery Inc. is seen investigating a case involving a demon ghost. However, due to a misunderstanding, they end up capturing a regular person instead of the actual culprit. This leads to them losing their confidence and deciding to retire from mystery-solving.
Later on, Vincent Van Ghoul, a former ally of the gang, contacts them and informs them about an unfinished investigation related to Daphne, Shaggy, and Scooby's past. The investigation is about the Chest of Demons, which they were tasked with guarding. However, they failed to prevent the 13th Ghost from escaping, and it has been causing chaos ever since.
The gang agrees to help Vincent in catching the 13th Ghost, but they are warned that it is a very dangerous task. Along with Vincent, they journey to the remote town of Grimwood, where they find a group of female students who are descendants of the original owners of the Chest of Demons.
As they start investigating, they encounter various obstacles and challenges, including the 12 other ghosts that they must capture to complete the set. They also find out that there is a traitor amongst them who is working with the 13th Ghost.
Finally, after a series of thrilling adventures, they manage to capture the 13th Ghost and complete the Chest of Demons. The gang is praised for their bravery and is reinstated as the Mystery Inc. team.