Dr. Phibes plans to avenge his unhappy childhood by unleashing a stampede of genetically engineered chicken bulls on the Western Tri-State Fair. Shaggy and Scooby must now find a way to stop him, while facing purring vultures, a hissing goat, and an 11-foot cross-eyed rooster.
Dr. Phibes, tired of being outsmarted by our heroes, revises his nano formula to increase his IQ. It also inflates his head. Now, Shaggy and Scooby must stop him from releasing a gas that will drastically lower the world's intelligence.
After being evicted from the lair by his evil clone, Dr. Phibes moves in with Shaggy and Scooby. However, due to Phibes' incessant crank calls, the clone decides to do something that even the real Phibes would never consider -- activate their Doomsday machine.
On the verge of a mental breakdown, Dr. Phibes decides to take a vacation while Shaggy and Scooby win tickets for a Mexican cruise -- the exact same cruise that Phibes is on.
After learning Dr. Phibes consumed a large quantity of the new nano-tech formula, Shaggy and Scooby must quickly devise a plan to rid of every nano-bot inside his body before Phibes becomes completely unstoppable.
When Shaggy's rich Uncle Albert goes missing and is presumed dead, Shaggy receives an inheritance, which he uses to upgrade the Mystery Machine so it can transform itself into other types of vehicles. Before disappearing, Uncle Albert made some enemies and it is up to Shaggy and his trusty canine, Scooby-Doo, to defeat those enemies, the most dangerous of whom is evil Dr. Phineas Phibes. Armed with the upgraded Mystery Machine, a loyal robot servant and their new riches, Shaggy and Scooby must stop Dr. Phibes' evil plans and save the world.