Five years ago a massive explosion released nanites into the atmosphere, infecting every living thing on Earth. These nanites randomly activate inside their hosts, mutating the subject into monsters known as E.V.O.'s (Exponentially Variegated Organism). They are usually mindless creatures that are a threat to everything around them. To combat the E.V.O. threat, the organization known as Providence was created to capture, cure, or kill them.

Rex is a 16-year-old amnesiac teenager who, like everyone else, is infected with nanites. However, unlike most E.V.O.s, Rex can control his nanites, allowing him to manifest a variety of powers and even cure others of their mutations. Working with Providence under Agent Six, he helps stop the E.V.O.s as they appear.

Working against Providence is the mysterious Van Kleiss, an E.V.O. with connections not only to the event which released the nanites, but to Rex as well.