The novel is told from the perspective of Alec Zander, a cartoonist who has settled on the small island of Antioch off the Atlantic coast of France, where he lives in semi-isolation.

When communications temporarily go down and rumours emerge about nuclear war, he comes in contact with a secret society, les amis d'Empédocle (lit.

[1] Christophe Henning of La Croix called the book "epic and chilling" and wrote that it contains both criticism and humour.

[2] Khadija Khalifé of The French Review wrote that On the Isle of Antioch repeats the message from Maalouf's 2019 book Adrift: How Our World Lost Its Way, where human wisdom is the solution to threatening apocalypse.

[1] Kirkus Reviews called it "an elegant portrait of a dying world" and compared Maalouf to Arturo Pérez-Reverte in the way he handles speculative fiction.