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The story begins with Yggdrasil, a popular online game which is quietly shut down one day; however, the protagonist Momonga decides to not log out. Momonga is then transformed into the image of a skeleton as "the most powerful wizard." The world continues to change, with non-player characters (NPCs) begining to feel emotion. Having no parents, friends, or place in society, this ordinary young man Momonga then strives to take over the new world the game has become.

Sora and Shiro are a pair of siblings, brother and sister, who are well known as brilliant. Yet they are NEETs - useless to society, and (Not in Education, Employment, or Training) - and even worse they are completely house-locked shut-ins (hikikomori!). Their reputation as gamers has spawned urban legends all over the Internet. These two gamers even consider the real world as just another "crappy game." One day, they are summoned by a boy named "God" to an alternate world. There, God has prohibited war and declared this to be a world where "everything is decided by games"—even national borders. Humanity has been driven back into one remaining city by the other races. Will Sora and Shiro, the good-for-nothing brother and sister, become the "Saviors of Humanity" on this alternate world? "Well, let's start playing."

Japan engineered an armed powered exoskeleton "Infinite Stratos" (IS) and it became the mainstream of weapons. Since only women can operate IS, women dominate the society over men. Orimura Ichika is a 15 year old boy and accidentally touches an IS placed in the IS pilot training school. He is found to be the only man who can operate IS and forced to enter the training school. Ichika's busy school life surrounded by girls has begun.

The school romantic comedy revolves around a second-year high school student named Sorata Kanda who lives in Sakurasou, the dormitory for problem children at Sorata's school. One day, Mashiro Shiina—a cute girl who happens to be also a cosmopolitan, brilliant artist—moves into Sakurasou.