As a young child, Takashi Natsume believed his ability to see youkai to be nothing but a curse. Now a high school student, Natsume has managed to heal from his old wounds and form unbreakable bonds with humans and youkai alike. Natsume's newfound friendships—including the one with his spirit bodyguard Madara, nicknamed "Nyanko-sensei"—are often interlaced with his duty to return the names of the spirits written inside the Book of Friends, his late grandmother Reiko's keepsake. While more remarkable youkai reach out to him, Natsume discovers that he still has much to learn about the world that surrounds him.

As introverted colleagues at a travel agency in Tokyo, Takuya Oohara and Rika Honjouji both cherish their happily single lives. After work, home is where they feel most at ease: Takuya unwinds with his cat, while Rika studies various maps. However, an uncertain future looms over their treasured tranquility when their company plans to open a branch office in Alaska within one year and transfer an unmarried employee there. During a day off, Takuya and Rika accidentally meet and, despite never having spoken before, open up to each other about their relocation fears. Feeling encouraged by Takuya facing the same predicament, Rika suddenly proposes a daring solution—to pretend to be engaged for 365 days. Takuya accepts, but little do the two know that the path to marriage may, in many ways, change forever the very lifestyles they struggle to preserve.

One day, Hitoyoshi Yokoya wakes up to a mysterious nameless girl dressed as a maid ringing his doorbell, asking to be his servant. With her former master referring her to the Yokoya household, she offers her expertise as an assassin. Intimidated by her background, Hitoyoshi tries to send her away; but when she leaves something behind, he rushes to return it to her and is nearly hit by a truck in the process. With her fast reflexes, the girl saves him just in time, and Hitoyoshi ends up taking her in. Ironically, the maid lacks any skills apart from the art of killing she has perfected since childhood. Nevertheless, Hitoyoshi welcomes the girl with open arms, encouraging her to leave her monochromatic past behind and experience a normal life. To seal the deal, Hitoyoshi names her Yuki, marking the beginning of her path to redemption and happiness.

Not long after forming their partnership, detectives Ron Kamonohashi and Totomaru Isshiki have proven adept at solving various cases together. However, the two are further motivated to continue their work when they discover that the House of M—an infamous crime syndicate—orchestrated Ron's expulsion from the prestigious Detective Training Academy BLUE five years prior. It appears that this group is also linked to Ron's mysterious ability that causes those around him to lose their lives, a phenomenon which Ron is desperate to stop. A member of the House of M soon starts to commit boastful serial murders around Shibuya as an act of provocation toward Ron. Consequently, the investigative pair must do their best to apprehend the culprit for the sake of justice as well as learning more about Ron's dark past and present condition.