The story of Kamen Rider 555 unfolds in a world where the powerful Smart Brain corporation secretly pursues global domination. Their plan involves the Orphnochs, beings described as the next stage in human evolution. These Orphnochs are created when a person who has died, or come close to death, resurrects with powerful new abilities. However, their existence is tragically unstable, as their genetic structure will eventually break down, leading to their death. To combat this fatal flaw, Smart Brain seeks to awaken the Orphnoch King, a being with the power to save them.

In pursuit of this goal, Smart Brain develops three advanced transformation systems known as Rider Gears: Faiz, Kaixa, and Delta. These armored suits are designed to be wielded by Orphnochs to protect their King. However, the gears are stolen by a renegade former executive of Smart Brain who sends them to his foster children in the hopes they can stop the corporation's plans. This act sets the stage for a chaotic conflict where the gears fall into unexpected hands.

The central protagonist is Takumi Inui, an aloof and seemingly indifferent drifter. He becomes the unwilling wielder of the Faiz Gear after using it to save a young woman named Mari Sonoda, one of the foster children meant to receive the device. Takumi transforms into Kamen Rider Faiz, fighting to protect others even as he tries to distance himself from any responsibility. Mari is determined and spirited, seeking answers from her estranged father, the president of Smart Brain. She is joined by the kind-hearted Keitaro Kikuchi, a gentle young man who runs a laundry business and offers the group a place to stay and a sense of normalcy.

The narrative is given a powerful counterweight through the story of Yuji Kiba. After a horrific car accident leaves him in a coma, he awakens two years later to find his life destroyed: his parents are dead, his girlfriend has married his brother, and his home is gone. Overcome with grief and rage, he resurrects as the powerful Horse Orphnoch. Yuji is a tragic figure who longs to retain his humanity and coexist peacefully with humans, bringing him into conflict with Smart Brain's agenda. He is joined by Yuka Osada, a bullied girl who becomes the Crane Orphnoch, and Naoya Kaido, a bitter former music student who becomes the Snake Orphnoch. Together, this trio of renegade Orphnochs tries to find their own path, often clashing with and sometimes aiding the human Riders.

The arrival of Masato Kusaka, another acquaintance of Mari, drastically complicates the struggle. He seizes the Kaixa Gear, which is known to be deadly for anyone who is not an Orphnoch. Kusaka is manipulative, obsessive, and harbors a deep infatuation with Mari, viewing anyone close to her, especially Takumi, as a rival to be eliminated. His ruthless and self-serving nature makes him a constant wild card, often creating more conflict than the Orphnochs themselves. The third belt, the Delta Gear, eventually appears, but its immense power is difficult to control, leading to a rotating cast of users.

Opposing both the Riders and the renegade Orphnochs is the elite force known as Lucky Clover, four of Smart Brain's most powerful and loyal Orphnochs. Their mission is to retrieve the Rider Gears and ensure the safe awakening of the Orphnoch King, who manifests in a young, innocent boy named Teruo Suzuki. As the series progresses, the lines between human and monster blur. Characters are forced to confront difficult questions about identity, loyalty, and what it truly means to be human. Takumi and Yuji, despite being natural enemies, share a deep, unspoken bond of loneliness and a desire to protect, leading to moments of uneasy alliance and heartbreaking betrayal.