While running a spy network from their elementary school, five unpopular misfits combine their talents and use cutting-edge gadgetry to fight evil around the world.

When a virus infects Arlington, Virginia, home of NERDS headquarters, transforming victims into criminal masterminds, it is up to Flinch to stop its spread by miniaturizing himself and entering the head of the Villain Virus's creator, Heathcliff Hodges.

When Ms. Information kidnaps the President's daughter, it is up to twelve-year-old Ruby, also known as Pufferfish, to use her super-nanobyte-enhanced allergies in leading the NERDS' investigation.

Orphans Sabrina and Daphne Grimm are sent to live with an eccentric grandmother that they have always believed to be dead.

With the help of a long lost relative, and a little magic, Sabrina Grimm and her sister Daphne try to find out who has kidnapped their parents and rescue them.