In the novel's somewhat dystopian world, human personalities can be stored digitally and downloaded into new bodies, called sleeves. Most people have cortical stacks in their spinal columns that store their memories. If their body dies, their stack can be stored indefinitely. Catholics have arranged that they will not be resleeved as they believe that the soul goes to Heaven when they die, and so would not pass on to the new sleeve. This makes Catholics targets for murder, since killers know their victim will not be resleeved to testify. A UN resolution to alter this legal position forms one strand of the novel's plot, to allow the authorities to sleeve a deceased Catholic woman temporarily to testify in a murder trial.

Carl Marsalis is a selectively bred human ("genetic variant") known as a "Thirteen", characterized by high aggression and low sociability. Bred to serve in a military capacity, Thirteens were later confined on reservations or exiled to Mars. Carl, having won by lottery the right to return from Mars, works covertly, tracking down renegade Thirteens.

Some 30 years after Altered Carbon, Takeshi Kovacs is now serving in Carrera's Wedge, a mercenary organisation which joins a corporate war on a distant colony, Sanction IV, and fights the rebellion against the corporate-sponsored government. While having his latest body repaired after a disastrous campaign, Kovacs is approached by pilot Jan Schneider, who is looking for protection for an expedition to exploit a Martian artefact discovered just before the war broke out. "Martian" artefacts have been known for many years at this point, one of them being featured in Altered Carbon. Later it is realised that the "Martians" were not from Mars, but were a technologically advanced species that left artefacts on many planets, including Mars and Kovacs' home world.

A coup in Cambodia. Guns to Guatemala. For the men and women of Shorn Associates, opportunity is calling. In the superheated global village of the near future, big money is made by finding the right little war and supporting one side against the other–in exchange for a share of the spoils. To succeed, Shorn uses a new kind of corporate gladiator: sharp-suited, hard-driving gunslingers who operate armored vehicles and follow a Samurai code. And Chris Faulkner is just the man for the job.

An ex-corporate enforcer, Hakan Veil, is forced to bodyguard Madison Madekwe, part of a colonial audit team investigating a disappeared lottery winner on Mars. But when Madekwe is abducted, and Hakan nearly killed, the investigation takes him farther and deeper than he had ever expected. And soon Hakan discovers the heavy price he may have to pay to learn the truth.

Marsalis is one of a new breed. Literally. Genetically engineered by the U.S. government to embody the naked aggression and primal survival skills that centuries of civilization have erased from humankind, Thirteens were intended to be the ultimate military fighting force. The project was scuttled, however, when a fearful public branded the supersoldiers dangerous mutants, dooming the Thirteens to forced exile on Earth’s distant, desolate Mars colony. But Marsalis found a way to slip back–and into a lucrative living as a bounty hunter and hit man before a police sting landed him in prison–a fate worse than Mars, and much more dangerous.

In a world where the real and virtual are one and the same and the dead can come back to life, the damsel in distress may be none other than the infamous Quellcrist Falconer, the vaporized symbol of a freedom now gone from Harlan's World. Kovacs can deal with the madness of AI. He can do his part in a battle against biomachines gone wild, search for a three-centuries-old missing weapons system, and live with a blood feud with the yakuza, and even with the betrayal of people he once trusted. But when his relationship with the Falconer brings him an enemy specially designed to destroy him, he knows it's time to be afraid.