Hank and Dean Venture, with their father Doctor Venture and faithful bodyguard Brock Samson, go on wild adventures facing megalomaniacs, zombies, and suspicious ninjas, all for the glory of adventure. Hank and Dean Venture are relatively identical twins, only born six minutes apart, who live for the thrill of adventure. Their dated vocabulary and high-pitched voices are intentionally annoying, especially to their father, Doctor Venture, a boy genius turned mediocre scientist who hates everything about his life. In the midst of this conflict is Brock Samson, a man of swift neck-breaking action. Preferring to resort to his brawn instead of his brain, Brock is simple but effective, and does a better job at taking care of the kids than Doctor Venture.
Somebody has been kidnapping the world's super-scientists and super-villains and taking them to a super death camp. But who? And to what end? The OSI, SPHINX, The Guild of Calamitous Intent and The Revenge Society must put aside their differences and convene a secret think tank to solve a mystery of epic proportions.
Hank and Dean graduate from their education beds, (although Hank did not receive his diploma and Dean did) and look into colleges. Hank rebels and tries to join Sphinx. Meanwhile, Phantom Limb breaks out of the Guild's dungeons and teams up with Professor Impossible to seek revenge once more.
Brock, Hank, and Dean are shrunk to microscopic size and is injected into Dr. Venture's body to discover why he is paralyzed. The Monarch's buys a "Butter-Glider", a new butterfly-themed personal flying device and becomes creepily obsessed with it, driving an emotional wedge between him, his henchmen, and his wife, and Henchman #21 continues his rise to power.
21 seeks revenge on Brock Samson for the murder of 24. Meanwhile, the Monarch has a sinister plot to finish off Dr. Venture once and for all...
The Order of the Triad must banish and destroy a demon spawned from hell... While the Order of the Triad battle a Hellbeast, Triana accidentally stumbles into another plane of existence.