By the 19th century, humanity has cultivated technology enabling the reanimation of corpses. Unable to experience individual thoughts or emotions, the corpses are programmed by humans to act as laborers in various occupations. This newfound technology, however, comes with a catch. Science may be able to restore the corpses' ability to move, yet it cannot return what every corpse loses at death: the soul. But Doctor Victor Frankenstein, who vanished shortly after his revolutionary work on corpse reanimation, is said to have revived the only corpse in possession of a soul. In pursuit of this scientific knowledge, London medical student John Watson hopes to fulfill his promise to his late partner, Friday. After being scouted by a government agency, Watson is on a hunt to obtain Frankenstein's notes, which he believes hold the key to the secrets of the soul. During his search, Watson uncovers the harsh realities of the developing corpse technology and the price he must pay to advance his research.

Tanis, a child genius, is the youngest son of two mad scientists. His family has spent their lives withdrawn from normal society living on an isolated island, where the couple conducts experiments on Tanis' siblings that result in them gaining abnormal abilities. However, this activity is put to a stop when they are caught and arrested. Tanis is brought by government officials to a more populated island, alongside his four siblings: Snow, a dog-human hybrid; Ashise, a plant-human hybrid; Aisley, a spider-human hybrid; and Suishi, a mind-reader. Being the only one who has not been genetically modified, Tanis takes on the responsibility of adapting his siblings to society, all while trying to conceal their' distinctive characteristics.

Amid the desolate remains of a once-thriving city, only the rumbling of a motorbike breaks the cold winter silence. Its riders, Chito and Yuuri, are the last survivors in the war-torn city. Scavenging old military sites for food and parts, the two girls explore the wastelands and speculate about the old world to pass the time. Chito and Yuuri each occasionally struggle with the looming solitude, but when they have each other, sharing the weight of being two of the last humans becomes a bit more bearable. Between Yuuri's clumsy excitement and Chito's calm composure, their dark days get a little brighter with shooting practice, new books, and snowball fights on the frozen battlefield. Among a scenery of barren landscapes and deserted buildings, Shoujo Shuumatsu Ryokou tells the uplifting tale of two girls and their quest to find hope in a bleak and dying world.

In the year 2200, a new Cold War between two forces is set to end with a peace treaty. However, one side is hiding a dark secret, which results in numerous tragedies in the following months. In the wake of a crisis, a paramilitary team is founded to steal information at the center of the conflict.