One day, when Remu Mikage is on a video call with his sister, Shiki, who has traveled to the futuristic Okinotori-island Mega Float City for school, she confesses that both the audio and visuals of her are completely artificial. In order to be more efficient in her studies, Shiki has used neural-linked nanomachines to upload her consciousness onto a computer and is storing her physical body in a "body pool." While shocked, Remu is supportive of his sister's decision, until the disaster known as the "Early Rapture" happens. The Early Rapture causes everyone who has uploaded their consciousnesses to either fall into a coma or perish. Remu visits his sister's empty apartment one last time, but is shocked when Shiki arrives at the door. With no memory of her family or past, and being pursued by a violent group of researchers, Shiki and her brother are forced to flee using her newfound power of nanomachine manipulation.

In a future governed through the lens of a camera, where people eat synthetic food and pursue an online existence in lieu of physical contact, a group of children begin meeting up in the real world. The aloof Ayumi Kono, the genius hacker Mio Tsuzuki, and the socially awkward Hazuki Makino set out to find the fourth member of their group, Yuko Yabe, who has gone missing. With the help of Myao Rei, an unregistered citizen proficient in martial arts, they are able to find Yuko. However, when their situation takes a sudden turn for the worse, the group stumbles headlong into a dark mystery that challenges everything they know about their world.

A young girl named Tomoko visits the Hiroshima Peace Memorial. There she has a mysterious meeting with Sadako, the little girl who was 2 years old when the U.S. dropped the bomb on her city during WWII and 11 when she died from the effects of radiation poisoning. Sadako takes Tomoko on an eye-opening journey.

The cyborgs are no longer on duty, they live normal lives until a mysterious space ship lands on earth. The only survivor on the ship warns about an evil conqueror called Zoa that wants to conquer the universe, which means the cyborgs are back in action...