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. Yuji will have to deal with the horrors of fighting a bloody war as he and the fighters from Second Earth look to survive. Will they be able to win back Earth without losing their humanity?

The story takes place in an alternate reality based in the year 1996, where humanity is advanced enough to develop long-range space travel, as well as bases on both the Moon and Mars. However, the Cold War tensions between the United States and the Soviet Union have not ended; rather, they've escalated as both sides build military facilities in space, and the shadow of nuclear conflict looms over humanity, both on and off Earth. Meanwhile, on the Red Planet, an exchange program created by the United Nations to promote peace and understanding is about to begin; the Cosmic Culture Club, consisting of 16 boys and girls, as well as their instructor Elizabeth, arrives at the UN Mars base. Among the passengers is Anna a 14-year-old girl who serves as the narrator for the story. Suddenly, four unidentified humanoid robots classified as Super Powered Tracers are detected, engaged in fierce combat with each other. The UN base is caught in the crossfire and quickly destroyed, killing all but six members of the Cosmic Culture Club—Elizabeth, Arthur, Roan, David, Simone and Anna, and leaving them stranded on an inhospitable planet that has suddenly become a battlefield. As the battle ends, the lone SPT standing lands next to the terrified group and opens up revealing a pilot, who simply announces to them, Earth is at stake.

Teropterids are evil beasts which pose as humans and live only to drink human blood. Fortunately for the human world there are groups dedicated to destroying them. A brooding and mysterious girl named Saya is the best teropterid slayer there is, and now, in 1960s Japan, she is sent to a U. S. army base which may be infested... (Source: ANN)

Peaceful schoolgirl by day, fearsome monster slayer by night, Saya Kisaragi is leading a split life. Equipped with a ceremonial sword given to her by her father for sacred tasks, she vanquishes every monster who dares threaten her quiet little village. But all too soon, Saya's reality and everything she believes to be true is tested, when she overhears the monsters speak of a broken covenant—something she knows nothing about. And then, unexpectedly, a strange dog appears; it asks her to whom she promised to protect the village, curious as to what would happen if she were to break that promise. Tormented by unexplainable visions and her world unraveling around her, we travel with Saya through her struggle to find a way to the truth in a village where nothing is as it seems.