The story is set in a world where artificially intelligent, emotional androids called Phiroids were developed before a rapid decline in human civilization.

An emotionless young man named Rei with a mechanical right hand is cared for by a girl in a small town as he gradually learns how to express emotions.

Like Key's 2004 game Planetarian: The Reverie of a Little Planet, Harmonia is defined as a "kinetic novel", since its gameplay offers no choices or alternate endings.

[1] A rapid decline in human civilization began once the population hit its peak of 10 billion, caused in part by pollution and war.

[3] Artificial memories could also be implanted into the Phiroids, making them highly desirable, leading them to be produced in numbers that eventually rivaled the human population at a time when the birth rate was already in decline.

The gameplay is spent on reading the story's narrative and dialogue and follows a linear plot line; this is what Key refers to as a "kinetic novel".

Throughout the game, the player encounters CG artwork at certain points in the story, which take the place of the background art and character sprites.

[11] To pay Shiona back for her kindness, Rei sets out to repair a broken music box containing a song her brother had composed.

Rei goes to the library to find a book to help in the repairs and meets the librarian, a little girl named Tipi (ティピィ, voiced by: Misaki Kuno) who is constantly sad.

With the help of the townspeople, Rei also repairs a projector to play a film directed by the son of Madd (マッド, voiced by: Kenta Miyake), the owner of the general store.

Rei puts Shiona and Tipi in cryogenic pods before leaving with the music box in an attempt to find a world where humans and Phiroids can coexist.

[12] In 2010, Nakamura had submitted a scenario titled Todoketai Melody (届けたいメロディ) to Visual Arts' Kinetic Novel Awards.

[13] Itaru Hinoue served as the art director and character designer, which marked her last contribution to Key before resigning in September 2016.

[22] Prototype released a Nintendo Switch port worldwide on October 20, 2022 with text support for Japanese, English and Chinese.