After hearing Shaggy and Scooby comment on how he isn't good at butlering or much else, Robi thinks he's failed at his job and leaves. He leaves Sparky to take his place transmitting Uncle Albert's messages. Soon Agents 1 and 2 find him at his new job in a criminal hangout. Now, unless Shaggy and Scooby stop him, Dr. Phibes will be able to gain access to Uncle Albert's inventions, as well as discover where he's hiding. And to make matters worse, Robi won't survive the downloading process.
Dr. Phibes and his agents and techies make a DVD of a horror movie with real monsters, and thanks to Robi's new 4-D entertainment system, the monsters invade Shaggy and Scooby's home. A pig named Bacon from a trailer Agent 2 was obsessing about also lounges around, and Scooby and Shaggy work on a way to stop the monsters and Phibes before he can make copies of the DVD.
Dr. Phibes' latest world domination plan includes producing a massive army of nano clones. Each clone represents a different part of Phibes' personality. Shaggy and Scooby must face their toughest task yet, but little do they know that if Scooby consumes too much of the nano formula, the more likely he will become immune to its effects. Meanwhile, Robi's spring cleaning creates even more chaos for everyone.
Now fully nano-powered, Dr. Phibes plans to blow up his new remote volcanic lair which would cause nuclear winter and mass extinction around the world. Meanwhile, Shaggy arms himself with Uncle Albert's super suit as he and Scooby must infiltrate the lair to once again put a stop to Phibes' evil plans.