On a sunny July day in the 41st year of the Shinka Era, Jirou Hitoyoshi is tasked with covertly listening in on a secret meeting between a top government scientist and an industrial spy. However, his cover is blown, and the spy reveals himself to be an alien in disguise. Amidst the ensuing chaos, Jirou enlists the aid of cafe waitress and magical girl Kikko Hoshino, one of many "superhumans" who blend into society and secretly protect humanity from extraterrestrial threats. As a member of the government agency known as the Super Population Research Laboratory, Jirou has the dual task of protecting superhumans that defend humanity and disposing of any deemed too dangerous to live. Having proven herself a worthy ally, Kikko is invited to join the agency as its newest recruit. Fast forward five years: disapproval and distaste for superhumans are now commonplace in Tokyo. From government corruption and conflicting ideas of justice, to the morality of superhuman rights, the relationship between humans and the supernatural minority balances precariously in a world pervaded by whispers of unrest and unease. Under mysterious circumstances, Jirou has betrayed the agency, and is now a fugitive on the run. As he skulks through the rainy back alleys of Shinjuku, he is pursued by the very same superhumans that he himself once recruited.

Titans from outer space, life forms from a mystical world, phantoms and goblins from ancient times, cyborgs created by scientists, relics that rose out of the ruins of ancient civilizations. In another Japan, it's not just a question of "what if"—it's a reality. Some of the superhumans choose to keep their identities a secret, while others bask in their superhuman fame. Jiro Hitoyoshi, member of the Superhuman Bureau, keeps track of their doings.

After living together for three years, Misaki Takahashi and Akihiko "Usagi" Usami's relationship has been progressing smoothly. However, all great relationships have problems, and theirs is just beginning. With a new rival on the horizon, Usagi worries about Misaki's feelings towards him. Meanwhile, Ryuuichirou Isaka has always loved to intrude on Misaki and Usagi's love life, but his own love life hasn't been all smooth sailing—Isaka and his secretary Kaoru Asahina have been dating for a few years; however, Asahina prefers to keep their professional and private lives separate, often leading to troubled waters between them. As for Nowaki Kusama and Hiroki Kamijou, now that their careers are finally taking off, they hardly see each other anymore. With the time they spend together lessening, doubts and insecurities threaten to creep in between them. On the other hand, the 17-year age gap between Shinobu Takatsuki and You Miyagi has been a constant barrier in their relationship, but as they learn more about each other, their self-consciousness continues to fade. The beloved couples of Junjou Romantica, Junjou Egoist, and Junjou Terrorist are back again, this time with a new addition: Junjou Mistake!

In a world of magic and monsters, Krylancelo Finrandi and his foster sister Azalie Cait-Sith were once promising students of sorcery, prodigies at the famous Tower of Fangs. But an experiment gone horribly wrong warps Azalie's appearance, trapping her in the form of a dragon. Elders at the Tower—more interested in preserving their reputation rather than their students' lives—drive off the transformed Azalie and cover up the incident. Outraged, Krylancelo strikes out on his own, taking the new name of "Orphen" and vowing to return Azalie to her normal state. Five years later, Orphen's quest has stalled. A chance encounter brings him face to face with Azalie again, but he still has no way to restore her body. And with a hostile group of sorcerers hunting her down, he may be running out of time. The past and present collide as Orphen tries to find how to save Azalie from their former teachers and friends.