Buddy is kidnapped by Tom Cruise, who plans to sacrifice him in a Scientology ritual. A group of Kabbalists rescues Buddy, and Ashton Kutcher and Demi Moore take the dogs home. The dogs end up doing stunt work for Bruce Willis, but Cruise comes back for Buddy, starting a clash between the Scientologists and Kabbalists.
After Tara Reid announces the official end of her career, Buddy and Woof end up at a rehab facility with her. That's where they meet Mariah Carey, Russell Crowe and Janet Jackson, as well as Andy Dick, who helps the dogs escape.