The novel follows protagonist Pierce Moffett as he continues his book project begun in The Solitudes about the Renaissance and Hermeticism, while dealing with a stormy relationship with his girlfriend Rosie Ryder.

The novel's title derives from De la Démonomanie des Sorciers a book purporting to be about demonology intended for would-be exorcists written by sixteenth-century French Jurist and politician Jean Bodin.

Thematically, the novel deals with the high numbers of demonic possessions and encounters with sorcery reported in the seventeenth century, precipitating a rise in dogmaticism among both Christians, Muslims and scientific thinkers at the time.

In the Author's Note, Crowley cites the research of Nuccio Ordine, Angelo Maria Ripellino, Brian P. Levnack, Carlo Ginzburg, Ioan P. Culianu, and Deborah Vansau Mccauley.

On a visit to New York, Beau Brachman is given a tract from a quasi-Gnostic sect, advocating the worship of the exiled "Sophia" as primordial to all religious practice, and the only escape from mankind's "imprisonment."

The chest Mary Philomel unlocked in the previous volume is revealed to not have opened, but responded with sounds resembling internal clockwork continuing for several years and coming to a stop at the novel's end.

[5] In The Village Voice, Elizabeth hand published an overview of the entire series, praising Daemonomania for its engagement of the darker aspects of the Renaissance, American spirituality, and Pierce's sexual drives.