After contracting hepatitis A, Ezaki Yuuichi has been confined to a hospital, away from his friends and family, much to his displeasure. To relieve his boredom, he has taken to sneaking out of the hospital, usually putting himself on the receiving end of a beating from his nurse. Upon meeting a girl his age also staying in the hospital, he is immediately captivated by her beauty. Akiba Rika's personality is not quite as captivating as her beauty however. In fact, she is rather selfish, moody, and bossy. But as the two spend more time with each other, they become closer, sharing the ordinary joys and trials of a budding teenage romance, even when darkened with impending tragedy—for Rika's condition does not leave her much longer to live.

Several months after a probe returning from Mars burns up during reentry, strange creatures dubbed Ancients begin to appear throughout Tokyo. Aggressive and dangerous, they cannot be killed with ordinary weapons. As scientists struggle to find the cause of their sudden appearance, the monsters wreak havoc across the world. Humanity finds hope in the form of the MARS suit—a new weapon developed to take down these enemies. The suit, however, can only be worn by those with specific DNA. Enter Takeru Hinata, an ordinary teen with a troubled past and one of the few capable of piloting the only weapon against the Ancients. With the help of the AAST, a special police force established to defeat the dangerous creatures, the young man battles against demons both personal and global whilst trying to discover the true nature of Earth's new aggressors.

Two years ago, Mitsuki Kouyama's friend, Eichi Sakurai, moved to America before she could confess her feelings to him. Though she cannot contact him, they made a promise to fulfill their respective dreams: Mitsuki wants to become a professional singer, and Eichi an astronomer. She hopes that one day her music will reach him across the world with a brilliance like that of the full moon. There is just one catch: Mitsuki suffers from throat cancer, which makes her voice quiet and singing strenuous. Her grandmother, who has a hatred of music, insists that Mitsuki undergo surgery to remove the cancer, but she refuses due to the risk of losing her voice. One day, two shinigami—Meroko Yui and Takuto Kira—appear to tell her that she only has one year left to live. This sudden revelation spurs Mitsuki into action, and she decides that with Meroko and Takuto's help, she will become a professional singer in the time she has left. Full Moon wo Sagashite follows the emotional story of Mitsuki and her shinigami friends as they discover what it means to sing—and ultimately, what it means to live.

As the season changes from spring to summer, Makoto Yuuki remains alongside the Specialized Extracurricular Execution Squad (SEES). The team continues to defeat Shadows large and small, but they now clash with a new enemy: Strega, a group of rogue Persona users who wish to keep the Dark Hour to their advantage—it seems that Strega may hold a clue to the Dark Hour's true nature. While SEES enjoys summer vacation in Yakushima, they are joined by Aegis, an amnesiac android designed to destroy Shadows. While she proves herself to be a powerful ally, she is inexplicably drawn to Makoto and constantly remains at his side. As they delve deeper into the mysteries of the Dark Hour, the nature of the mysterious connection that binds these two together is slowly unveiled.