After two years on the run following the Chihiro incident, Haruka Mizusawa is the last remaining Amazon as he is hunted the Competitive Creatures Control Center (4C). While cornered by the 4C squad leader Takeshi Kurosaki, Haruka is saved by his estranged foster sister Mizuki Mizusawa as the pair escape into a nearby lake. Haruka and Mizuki are found by a group of orphans and taken to their orphanage; The orphan Muku tends to Mizuki's wounds. Haruka meets orphanage director Einosuke Mido, who offers him a permanent home but warns him of an off-limits room in the facility. Within the off-limits room, the orphans offer their blood to a chained-up man.
As Mido and the children see off a newly-adopted orphan, a group of Amazons attacks the orphanage. Haruka transforms and fights them, and is shocked to see Mido fight alongside him as Kamen Rider Amazon Neo Alpha. The 4C squad finds the pair and attempts to kill them, but they are saved by the former members of the Nozama Peston Service, the original Amazon extermination team Haruka was a part of. The Nozama team members reveal themselves to have been sent by Haruka and Mizuki's mother, Reika. Not wanting to endanger the orphanage, Haruka and Mizuki depart with the team. Haruka crosses paths with the couple that had adopted an orphan, and discovers that they have killed and eaten the child - the orphanage is in reality a farm being an establishment secretly funded by 4C to create Amazons that are reared as livestock. Haruka attempts to warn the children, but discovers they're aware of their purpose and that the cells they grew were from the figure off-limits room: Haruka's nemesis Jin Takayama.
The Nozama team comes across a group of runaways from the orphanage living in an abandoned home. The children attempt to eat the Team, but are dissuaded by stories of their former Amazon teammates Haruka and Mamoru. But are forced to kill the runaways when their attempt to take them to safety is ruined by 4C's attack turning the Amazons hostile. Offered to a politician by 4C's chief Yugo Tachibana convinces a politician to gain support for the Amazon Livestock Project, despite having accepted being livestock, Muku regained her will to live and slaughtered the restaurant staff and the politician. Haruka arrives and consoles Muku, convincing her to live for herself. The two return to the orphanage and convince the other children to escape. A furious Mido begins killing the children and overpowers Haruka and Muku while Jin tricks an orphan into releasing him, wounding Haruka as he exacts revenge on Mido before proceeding to kill the remaining orphans. A dying Muku has Haruka devour her to heal his injuries so he can stops Jin, criticizing the man's Amazon-killing obsession regardless of their morality as their final battle ends with Jin's death.
Guilty overeating Muku, Haruka attempted to drown himself when a vision of Mizuki convinces him to live on as a protector. Meanwhile, the Nozama team and Reika inform Kurosaki of the Amazon Livestock Project as he joins their faction to remove Tachibana from 4C. Mizuki takes over as director of the orphanage and cares for the surviving children, waiting for Haruka to return. She convinces the surviving children to live their lives. Haruka looks at her through the window and departs.