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.
Team Venture, Conjectural Technologies and the Order of the Triad come together as Dean and Hank prepare to face an obstacle more intimidating than anything they've confronted before: a prom celebrating their "graduation" from high school.
Conjectural Technologies' newfound success hits a snag when Billy is kidnapped by the same mysterious benefactors who invested in their company, and SPHINX launches an investigation aimed at determining who is behind these dubious financiers.
The Monarch uses a machine to take control of Dr. Venture's mind and try to make him commit suicide, and Dr. Orpheus journeys into Dr. Venture's brain to save him.
Dean gets a summer internship with Impossible Industries, but unwittingly discovers Professor Impossible's dark ties to Phantom Limb, the Revenge Society and his new life as a supervillain.
With Dean off to New York for a summer internship, Hank is forced by his father to get a job, so he opens his own business. But when Dermott accidentally prompts him to take on solving the mystery of whether Brock really is Dermott's father, Hank dons a fabled fedora to become a private detective and discovers far more than he bargained for as a tangled mystery of sex, lies, and dirty secrets lands right in his lap.