In an alternate version of the United States in 2007, famous whistleblower Nils Ortega leverages his large online following to repeatedly attack the Bush administration, alleging a series of government cover-ups.

Nils's daughter, Cora Sabino, is a young college dropout living with her mother and her two younger siblings in Southern California, where her paternal aunt Luciana, a former federal agent, also resides.

Cora's family find themselves under constant supervision by agents of the U.S. government, including a high-ranking CIA official named Sol Kaplan.

The alien eventually catches Cora, implanting a tracking and communication device into her, using her as a human puppet to launch an infiltration of the Googleplex for unknown reasons.

Cora contacts Luciana in an attempt to convey Ampersand to his fellow aliens, called "amygdalines," who are being held in the Cheyenne Mountain Complex.

Nils and his followers continue to attack the government, embroiling George W. Bush in a scandal around an alleged attempt to cover up first contact with an alien species.

After surviving a car crash and severe injuries, Cora leaves the Genome with Luciana and attempts to track down Ampersand.

Cora awakes in a hospital, attended to by her mother and siblings, who have been released from government custody after Nils publicizes their abduction.

[3][4] Pajiba said it is "less about action than an exploration of communication across boundaries both human and deeply inhuman," and praised Ellis's handling of the book's themes, and that her "well-trained eye for the oddities and political edges of various cultural contexts comes in very handy.

"[4] Ryan Britt of Syfy Wire said that Ellis's authorial voice serves to "demystify" the story's central concepts: "Luckily, unlike so many 'big idea' sci-fi books, it's utterly unpretentious.

[6] Kirkus Reviews said the book "uses first contact to interrogate our tendencies toward xenophobia and prejudice and challenge our conceptions of what humanity means" and that it is "solid" but unpolished.

[8] In a video uploaded to YouTube on July 19, 2020, Ellis announced that the second and third books in the Axiom's End series would be released in summer 2021 and 2022.