Onegai Futago! is a story mainly revolving around three high school students: Maiku Kamishiro, Karen Onodera, and Miina Miyafuji. The three were drawn together by a photograph of their childhood home which later makes all of them seek out the house in the picture. However, the picture only has two children - a boy and a girl. Hence, only one of the girls, Karen or Miina, is related to Maiku. The only other identifying feature of the pair in the picture is that the boy and the girl have eyes of the same unusual color; a feature that furthers the ambiguity as all three of them have the same eye color.

The main concern of the male lead, Maiku, is that he is in love with both of the girls, and he does not know which one is his twin. In addition, the two girls are in love with Maiku, forming a love triangle of potential incest. The three main characters, mostly the two female leads, are in a predicament of wanting to discover their past versus the risk of losing a romantic relationship.

The events of the story are set after Onegai Sensei! and characters from the series appear in supporting roles throughout Onegai Futago!.