Blue Gender takes place in the not too distant future in a world where things have gone terribly wrong for humanity. Humans have been replaced at the top of the food chain by the Blue, a race of bug-like aliens that have colonized Earth and pushed humans aside. A space station, Second Earth, has been constructed as a safe haven for humans, with the hope of one day reclaiming the Earth once more.
Yuji Kaido was cryogenically frozen, having been suffering from a disease known as B-Cells. Once awakened, he joins a team of soldiers that have come to Earth to extract him. Unfortunately, nothing goes according to plan as they make their way back to Second Earth.