Mahiru Shirota firmly believes that simple is best and troublesome things should be avoided at all costs. It is troublesome to do nothing and regret it later—and this ideology has led the 15-year-old to pick up a stray cat on his way home from school. As he affectionately names the feline Kuro, little does he know that this chance meeting will spark an extraordinary change in his everyday life. One day, Mahiru returns home to find something quite strange: a mysterious young man he has never seen before. His subsequent panic results in the uninvited guest being exposed to sunlight and—much to Mahiru's shock—transforming into Kuro! Upon revealing himself as a mere lazy shut-in vampire, Kuro promises to leave once night falls. However, one disaster after another leads to Mahiru accidentally forming a contract with his new freeloader, dragging him into a life-threatening battle of supernatural servants and bloodthirsty beings that is anything but simple.

No longer concerned with military affairs, Yukichi Fukuzawa intends to act as a lone bodyguard-for-hire, making use of his deadly swordsmanship. However, things are not going as planned for his freelance business, and that is when he crosses paths with a mouthy boy named Ranpo Edogawa. While their initial interactions are intertwined with a bizarre murder mystery, the aftermath prompts the formation of the Armed Detective Agency. Presently, Ranpo finds himself chasing down a gifted individual with the dangerous ability to execute the perfect crime. But as the great detective unravels the case, he soon discovers an elaborate plot to obliterate the Agency in its entirety. Although forewarned of the trap, the Agency continue their pursuit of the criminals, only to end up framed for the crime themselves. Now branded as wanted terrorists, the remaining members must find a way to prove their innocence—even if they must turn to sworn enemies for assistance.

After succeeding in their winter conflict against Taiju Shiba and his Black Dragons, the Tokyo Manji Gang absorbs their group's remaining members. Due to his heroic courage and indomitable spirit, Takemichi Hanagaki should have accomplished his goal of defeating the tragic fate awaiting his girlfriend, Hinata Tachibana. In reality, Takemichi's troubles are far from over. Although Takemichi's actions have exposed Tetta Kisaki's treachery, the conniving schemer has found power elsewhere: Tenjiku, a dangerous gang led by the enigmatic Izana Kurokawa. Izana sets his sights on Manjirou Mikey Sano, pursuing a vicious interest in the Tokyo Manji Gang's aloof leader. In the future, Takemichi discovers that the machinations of Izana and Kisaki led to Mikey's moral ruin—a downfall that directly results in Hinata's death. Unfortunately, a terrible loss robs Takemichi of his time-leaping ability, stranding him in the past with one final chance to rescue everyone he loves.

During the 21st century, humanity attempted to colonize Mars by sending two species which could endure the harsh environment of the planet to terraform it—algae and cockroaches. However, they did not anticipate the species' remarkable ability to adapt. Now in the 26th century, a lethal disease known as the Alien Engine Virus has arrived on Earth, and the cure is suspected to be found only on Mars. The problem is, Mars in the present is overrun by creatures known as Terraformars, incredibly powerful and intelligent humanoid cockroaches that mutated from those originally sent to the planet. The Annex I team, consisting of a hundred men and women genetically enhanced with characteristics of powerful organisms from earth, has been sent to Mars on a mission to find the cause of the Alien Engine Virus and to help cure humanity—signalling the start of the crew's fight for survival.