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 a new agency, AiRBLUE's roster consists of voice actresses with absolutely no experience. Expecting to hone their skills and build courage at a gradual pace, the girls are taken aback when the head of their agency, Masaki Ootori, announces that they will be partaking in an audition for Bloomball—a popular sports manga receiving an anime adaptation. Despite all odds being stacked against them, each of the girls is now presented with a momentous chance to make their debut in the unrelenting world of voice acting.

Experienced voice actor Yasumi Utatane works hard to maintain her image as a pure and innocent idol to please her fans, even as she struggles to find more jobs in the industry. But Yasumi has a secret—she is actually Yumiko Satou, a high school girl who prefers loose clothes and flashy jewelry, a complete contradiction to her false professional persona. As Yasumi, Yumiko is finally offered an exciting opportunity to do a radio program alongside another up-and-coming voice actor she admires: Yuuhi Yuugure. In Yumiko’s eyes, Yuuhi’s cute looks and talented acting embody what a voice actor should be. As soon as they are introduced at the recording studio, however, Yumiko realizes that Yuuhi is actually her gloomy classmate, Chika Watanabe. Together, the pair commit to their radio program and slowly begin to open up. In supporting each other, Yumikoi and Chika gradually learn to be true to themselves.

Takato Saijou has held the title of "Sexiest Man of the Year" for five years running. He is an accomplished actor, with 20 years of experience under his belt, and is aware his good looks are well above average. Proud of his career, Takato regards the title as an appropriate indicator of his success. But when his reign is ended by acting newbie Junta Azumaya, who debuted only three years ago, Takato's initial shock gives way to jealous hostility. Even in the new drama that he has been cast in, Junta seems to have suddenly surpassed him; snatching Takato's usual spot of lead actor, Junta continually manages to get on his nerves. Most infuriating of all are the bright smile and kind words that accompany everything Junta does. All this animosity comes to a head, however, when Junta catches Takato in a rather vulnerable drunken state. Endangering his own public image, Takato confronts the junior actor with harsh words and angry comments—an opportunity Junta takes every advantage of. With the famous actor Takato Saijou now on video picking a fight with a co-star, Junta has the perfect means to blackmail him. Asking the price of his enemy's silence, Takato is shocked to find that his motivation lies far from advancing his career; instead, Junta's terms are those that can only be realized in the bedroom!