Effeminate fifth grader Shuuichi Nitori is considered by most to be one of the prettiest girls in school, but much to her dismay, she is actually biologically male. Fortunately, Shuuichi has a childhood friend who has similar feelings of discomfort related to gender identity: the lanky tomboy Yoshino Takatsuki, who, though biologically female, does not identify as a girl. These two friends share a similar secret and find solace in one another; however, their lives become even more complicated when they must tread the unfamiliar waters of a new school, attempt to make new friends, and struggle to maintain old ones. Faced with nearly insurmountable odds, they must learn to deal with the harsh realities of growing up, being transgender, relationships, and acceptance. Lauded as a decidedly serious take on gender identity and LGBT struggles, Takako Shimura's Hourou Musuko is about Shuuichi and Yoshino's attempts to discover their true selves as they enter puberty, make friends, fall in love, and face some very real and difficult choices.

The Fourth Industrial Revolution has led to the development of cutting-edge technologies that have rapidly evolved the world. As a result, schools have begun incorporating these technologies into their curriculum, leaving behind the ways of the old. One such institution is the elite Yuyu Girls' Vocational High School, where both Serufu Yua and her childhood friend, Miku Purin Suride, have applied. Although the tech-savvy Purin is accepted to Yuyu High, the accident-prone Serufu is rejected and enters the traditional Gatagata Girls' High School instead, driving a wedge into their friendship. On her way to class one day, Serufu gets into a bike accident, and Rei Yasaku, a passerby who attends the same school, fixes her damaged bicycle. Serufu later finds out that Rei has a passion for old-fashioned crafts and is the head of the school's Do-It-Yourself (DIY) Club—which is in danger of closing due to a lack of members. Realizing that this may be her chance to repair her relationship with Purin, Serufu joins the club in hopes of creating projects that could bring them together once more. As the DIY Club welcomes new faces, Serufu learns to build not only handicrafts but also new friendships along the way!

Second-year middle schooler Nao Takanashi loves her older brother Shuusuke to the point where she has developed a brother complex. Wanting her brother to see her as a woman, Nao makes advances toward him on a daily basis, which often results in Shuusuke succumbing to and encouraging more of her teasing. One day, while throwing away porn magazines from her brother's room, Nao finds an album containing his childhood photos—none of which include her. Having discovered the truth behind her family relationships, Nao becomes ever more affectionate toward Shuusuke. However, it does not take long for her dreams of monopolizing her brother to be put in jeopardy.

Hidomi Hibajiri is a disillusioned young girl who never takes off her headphones. Her whole life consists of going to school, helping out at her mother's cafe, and listening to music. And with nothing else to break the crippling monotony, she keeps her headphones on at all times. That is, until she is run over by a mysterious guitar-wielding woman. That same night, a robot barges into Hidomi’s room along with a boy from her class, Ko Ide, and the kids are chased around town together. They're saved by the guitar-wielding woman from before, but now Hidomi's got a horn growing from her forehead? Who knows where these robots are coming from, what kind of vespa woman this weird guitar woman is warning her about, or what this thing on her forehead is, but it doesn't look like Hidomi is going to be able to ignore all this with headphones!