When Dr. Girlfriend tells The Monarch her secret, they are then taken hostage by The Guild Tribunal, where we learn the past of the two villains.
When a deal with General Manhowers falls through, despite an elaborate production to impress him, Dr. Venture faces the possibility of having to sell the Venture Compound. Fortunately, Dr. Henry Killinger shows up to turn the company into an efficient super-science machine.
While reaching for more toilet paper, Billy falls and remembers his past. His journey to see Dr. Venture with game show host Pete White, how he loses his eye and hand and what truly was his relationship with Phantom Limb.
After a long period of boredom since the Monarch stopped arching the Venture family, a new villain has been assigned by the Guild to be their archnemesis: Sgt. Hatred.
Dr. Venture sets up a day camp for his childhood 'fanbase' and the Monarch uses the murderous moppets to monitor Venture's activities. Hank makes a new friend, much to Dean's chagrin.
While adventuring in the jungle, Dr. Venture is reunited with childhood friend Dr. Quymn. Dean attempts to solve a monster mystery and Hank falls in love with Quymn's twin daughters.
An accident involving a giant drill sends Dr. Venture and Brock into the basement of the Venture Compound, where Jonas Venture Sr.'s secrets have remained for thirty years.
The Monarch, having murdered his new arch-enemy, breaks into the Venture Compound while Dr. Venture is away. Dermott and Hank try to start a band, and spot what they think to be a UFO over the Compound.
Jonas Jr. turns the former archvillain headquarters, Spider Skull Island, into a museum devoted to his late father. Many villains and friends of the Ventures arrive, but things begin to go wrong after tensions between several of them arise, as well as when J.J. attempts to take the glory away from Rusty Venture.
The Monarch becomes Jonas Venture, Jr.'s new arch-enemy, and seeks out the assistance of the Office of Secret Intelligence, receiving two "amateur lepidopterists" and an "exterminator" to rid him of The Monarch. Henchmen 21 and 24 are sent on a mission with the new, perfect henchman, telling him throughout their adventure that he is sure to die.