When Earth's population drastically increased, humanity led by the United Nations attempted to colonize Mars. During the colonization, they discovered two alien technologies: the Bacillus and the Crusnik nanomachines. The colonists installed the Bacillus in their bodies which transformed them into Methuselahs. They installed the Crusnik in the bodies of four test tube babies: Seth, Cain, Abel and Lilith whose enhanced bodies were the only ones able to survive the procedure.
Continuing wars on Earth eventually led to "Armageddon", the apocalyptic event that happened 900 years before the start of the story, and the colonists returned to Earth to help with rebuilding, but when the colonists returned to Earth, a war broke out between the Methuselahs and the humans who had remained on earth. Abel, Cain, and Seth took the Methuselah's side—while Lilith supported the Vatican, which guarded humanity. During the war, Cain went insane and killed Lilith. In grief, Abel took her body to the Vatican where she was buried. Abel remained at her side, weeping for her, for 900 years.
At the start of the story, the vampiric Methuselahs, still a major political and military force, continue to wage war on the "Terrans", as they call regular humans. The Roman Catholic Church is a major military power determined to protect humans from the Methuselahs, with its seat of power based in the Vatican. The Methuselahs have their capital of Byzantium, which is surrounded by a field of particles to filter out UV radiation, protecting the Methuselah population.
Both groups use "lost technologies", such as airships, missiles, and computers, to engage in a cold war with one another. A third great power, Albion also plays a role in the war with its superior arsenal of lost technology and weapons and higher level of manufacturing ability versus the Vatican. The independent monarchy of Albion is a primarily human country, however the secret of their expertise in lost technology is found in the Ghetto, an underground city of enslaved Methuselah. It is these Methuselah who operate and manufacture the lost technology, but with the death of the Albion Queen, some of the enslaved vampires begin a rebellion for the freedom of all of the Ghetto residents.