After her inauguration, newly elected Vice President Natalie Maccabee is initiated into a covert world of danger by her chief steward, Malcolm Millar and Chief Justice Caleb Thorne. Contrary to what the public believes, the job of Vice President is far from ceremonial. In fact, enshrined in a secret version of the Constitution is a section endowing Natalie with her own secret agent, John Case, to be deployed in times of crisis. Natalie quickly finds herself in play when the daughter of FBI Director Stanton is kidnapped, and authorities are helpless in rescuing her.
One of John's old nemeses, terrorist Malik Ahmad, steals an arsenal of nuclear warheads and a scientist to activate them. John is forced to work with his enemy Olga Petrovka in order to destroy them and rescue the scientist. Meanwhile, Natalie and Malcolm endeavor to protect John's identity from an FBI investigation.
The cabal trail leads John to a lawless Mexican town, where he is drawn into a deadly feud between the local drug lord, nicknamed El Diablo, and the town's police chief, Luna. At the same time, Natalie probes into a romantic connection between her late husband, Steven, and the fiancée of her political adversary, Speaker of the House Miles Latham.
.John, incognito as a Secret Service Agent, accompanies Natalie on clandestine peace talks between the Mexican government and Marxist insurgents. When their helicopter is shot down by nefarious forces, the group is suddenly stranded in the middle of nowhere, hunted by some of the most dangerous men in the world.
John travels in disguise to a party on a reclusive billionaire's island in the hopes of stealing a dangerous high tech weapon, code named Geryon. At the same time, Natalie struggles to contain the latest fallout from the conspiracy against the President.