Set five years after the first season, the story follows the exploits of Chihiro, a boy raised by the genetically modified creatures known as Amazons. Chihiro also has the power to transform into Kamen Rider Amazon Neo. The series also follows Iyu, a girl who was killed by the Amazons but was later revived to become a genetically engineered weapon known as the Crow Amazon.
A group of youths, under the moniker 'Team X' are hunting down Amazons. Leading the charge is a mysterious blue Amazon, Neo.
Chihiro, who was brought back to 4C, wants to exterminate the Amazons with Iyu. In the battle with no emotions and only pain, Chihiro transforms to protect someone for the first time.
Haruka Mizusawa, Kamen Rider Amazon Omega, heads back into town. Returning from exile after Operation Tlaloc. He has found a new target in Iyu, who is a Sigma Type Amazon.
Chihiro wishes to act more human. He leaves the 4C compound to spend time with Iyu. Makoto Shido begins investigating an important incident, and encounters a person who he never thought he'd meet again…
As Mamoru (Mole Amazon) confronts his comrades from the past, Mizuki Mizusawa again encounters Haruka Mizusawa (Kamen Rider Amazon Omega). Can the 5 years which has separated them be filled?
Haruka Misuzawa (Kamen Rider Amazon Omega) continues his search for Mamoru, the Mole Amazon. HE soon encounters the extermination team, including Chihiro (Kamen Rider Amazon Neo) and Iyu, the Crow Amazon. Meanwhile, something strange is happening at the hospital where Emiri was admitted.
As Jin finally met Chihiro, all past events prior to Chihiro's birth and what came after Tlaloc alongside Jin and Haruka's war had finally been revealed.