All seems well until a rejuvenated Doctor Neo Cortex teams up with his old partner Doctor Nitrus Brio to invent a personal digital assistant, the "NV", that can control the minds of both mutants and bandicoots by transmitting bad Mojo, forcefully siphoned from Cortex's former boss Uka Uka.
Alt ser godt ud indtil en forynget Doctor Neo Cortex slår sig sammen med sin gamle partner Doctor Nitrus Brio for at opfinde en personlig digital assistent "NV'en", der kan kontroller tanker af både Mutanter og Bandicoots (punggrævlinge) ved at sende ond Mojo, ved at kraftigt tappe det fra Cortexs tidligere boss Uka Uka.