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.

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?

Yoichi Isagi was mere moments away from scoring a goal that would have sent his high school soccer team to the nationals, but a split-second decision to pass the ball to his teammate cost him that reality. Bitter, confused, and disappointed, Isagi wonders if the outcome would have been different had he not made the pass. When the young striker returns home, an invitation from the Japan Football Union awaits him. Through an arbitrary and biased decision-making process, Isagi is one of three hundred U-18 strikers selected for a controversial project named Blue Lock. The project's ultimate goal is to turn one of the selected players into the star striker for the Japanese national team. To find the best participant, each diamond in the rough must compete against others through a series of solo and team competitions to rise to the top. Putting aside his ethical objections to the project, Isagi feels compelled to fight his way to the top, even if it means ruthlessly crushing the dreams of 299 aspiring young strikers.

Saya Otonashi is a seemingly ordinary girl living a mundane life with her adoptive family in Okinawa City. In fact, her only peculiarities are suffering from anemia and being unable to remember any of her life beyond the previous year. However, Saya's forgotten past quickly comes back to haunt her—one night, she is attacked at school by a creature that feeds on human blood. Just when all hope seems lost, a mysterious man named Haji appears and fends off the creature temporarily. But when her rescuer forces her to drink his blood, Saya suddenly enters a trance and slays the monster with ease, using her own blood as a catalyst. Saya then learns of an organization named Red Shield, founded for the sole purpose of defeating the hellish beasts. Now Saya and Haji must work together with Red Shield to fight these fearsome monsters and unlock the secrets to the girl's past.