The game is set in 1969, 10 years after the original game. The game begins with a Soviet KGB slide show meeting showing that the main character from Destroy All Humans!, Cryptosporidium-137, is now deceased for unknown reasons. His clone, Cryptosporidium-138 (Crypto for short), made of more pure Furon DNA, is now taking his place and continuing to pose as the President of the United States. KGB intelligence reveals that Crypto-138 is the first and only Furon to have genitalia, referred to only as “The Package”. Seeing the Furons as a threat to the Soviet Union, the KGB destroy the Furon mothership with a nuclear missile.