Suda left Human Entertainment to form Grasshopper Manufacture following the release of Moonlight Syndrome, but the game remained an influence in his later work.

[4] One year after the events of Twilight Syndrome: Investigation, series protagonist Mika Kishii is attending high school in the town of Takashi when she begins to sense something very wrong with the people there.

Determining that all of these problems are a result of a psychic phenomena surrounding Takashi, Mika is joined in her investigation by Chisato Itsushima and Yukari Hasegawa.

As Mika tries to balance her investigation and leading a normal life, events being to escalate with violent incidents ranging from a mass suicide near her home to disturbing behavior from several of her close friends.

Eventually, Mika becomes troubled by hallucinations and strange dreams related to Takashi's plight, and several students die in suspicious circumstances, leaving the survivors increasingly disturbed.

In a post-credits scene, an unhinged Ryo is seen holding a paper bag on his lap containing the severed head of Kyoko, while Mika's face appears on a nearby television.

[5][6] The aim was to increase the frightening aspects of the game by making the violent incidents within the story random and caused by people rather than supernatural entities.

[2] During production, government restrictions around content in games and entertainment media were tightened due to the Kobe child murders and their resultant controversy.

[10] One reviewer from Famitsu magazine noted that those expecting the "simple school horror" of earlier titles would be shocked by the game's story.

[10] In a 2016 retrospective, Den Faminico Gamer criticized the characters and the lack of branching scenarios, feeling the game was linear and the speech choices had no consequence.

[17] Grasshopper Manufacture has borrowed settings and characters from Moonlight Syndrome for The Silver Case and some of their other work including Flower, Sun, and Rain.