Shaggy's uncle disappears and leaves Shaggy with millions of dollars, so Shaggy and Scooby-Doo go to the mansion he left for them and start exploring. They see some of his inventions and then Shaggy sees a note about how his new invention is trying to be stolen by someone and now he must go into hiding. Now Scooby and Shaggy have to go and solve another mystery.

After receiving an urgent holographic transmission from Uncle Albert, Shaggy and Scooby travel to Switzerland, using their new and improved mystery machine, in order to thwart Dr. Phibes' efforts in interrupting an anti-global warming conference. Once Phibes realizes he's being followed, he counteracts by sending one of his most dangerous agents after them.

Dr. Phibes' latest evil plot is to abduct three of the world's leading scientists in order to gain technologically advanced weapons. Shaggy and Scooby must prevent this by sneaking into the country club where the scientists are being honored and protect them at all costs. However, they also have to deal with Phibes' agents.

Shaggy and Scooby decide to throw a housewarming party, but their neighbor and president of the Housing Association, Thurston Havansimp, sets out on derailing their plans. He threatens to cite them with enough code and permit violations to evict them from their house and the neighborhood. Meanwhile, Dr. Phibes finds about the party and sends a deadly robot to the Shaggleford Mansion with orders to annihilate the dynamic duo.

Dr. Phibes plans on unleashing an evil computer virus into the nation's weapon defense systems, but Uncle Albert gets word of it first. While intercepting the virus, Shaggy and Scooby unknowingly release the virus into their in-house's computer system, which soon takes control of every appliance and utility in the mansion.

Dr. Phibes sets out to destroy the rainforest in search for the secret to eternal youth. Meanwhile, poachers try to stop Shaggy and Scooby.

Shaggy and Scooby are nominated for the "Mystery Solvers of the Millennium" award. However, at the ceremony, the mystery solvers begin disappearing one by one while Shaggy and Scooby must work fast to discover who's taking them before they're next.

Dr. Phibes decides to hit Shaggy and Scooby in their most vulnerable spot - their stomachs! He invents a hypnotic hibachi and then hires an evil chef to use it on them as they visit the set of their favorite cooking show, "Chefs of Steel".

Shaggy and Scooby meet up with Fred, Velma, and Daphne at a military base where Dr. Phibes' agents use their new invisible technology to steal weapons.

In order to gain immortality, Dr. Phibes plans on setting off a bomb at the end of the "Polar Bear 3000" race which will destroy all electronics across the world. Naturally, Shaggy and Scooby enter the race to make sure that he doesn't succeed.

Dr. Phibes is finally going to get his wish and become immortal! He has built a giant robot version of himself and plans to conquer the world with it. It is up to Shaggy and Robo-Scooby to put a stop to his big plans.

With the intention of finally stealing Uncle Albert's secret formula, Dr. Phibes assembles three of the most ruthless criminals in history to destroy Shaggy and Scooby.