It begins in Toronto, in the years after the smart drug revolution. Any high school student with a chemjet and internet connection can download recipes and print drugs, or invent them. A seventeen-year-old street girl finds God through a new brain-altering drug called Numinous, used as a sacrament by a new Church that preys on the underclass. But she is arrested and put into detention, and without the drug, commits suicide.

Lyda Rose, another patient in that detention facility, has a dark secret: she was one of the original scientists who developed the drug. With the help of an ex-government agent and an imaginary, drug-induced doctor, Lyda sets out to find the other three survivors of the five who made the Numinous in a quest to set things right.

A mind-bending and violent chase across Canada and the US, Daryl Gregory's Afterparty is a last chance to save civilization, or die trying.