Set in Rome, Nabatea, and Palmyra, the novel stars Marcus Didius Falco, informer and imperial agent.

The title refers to the hunt undertaken by Falco for a murderer, the last act of which takes place in Palmyra, as well as plays upon Falco's temporary employment as a playwright with a travelling theatre group.

In Last Act in Palmyra, Falco takes on a new spying mission for Vespasian to the east of the Empire.

Falco and Helena Justina travel to Petra, where they encounter a theatre group who have just lost their playwright due to drowning.

Joining them, Falco attempts to fulfill his various investigations, whilst at the same time write his new play, The Spook Who Spoke.