Cesare recruits a band of mercenaries with the help of Micheletto to seek revenge on the retreating French troops for burning the nunnery where his beloved Ursula lived; the Pope forges more strategic alliances and enriches himself in the bargain; Lucrezia joins Giulia's quest to aid Rome's poor.

Juan's triumphant return from Spain is marred by his unsuccessful siege of the Sforza castle; Lucrezia purposely scuttles a scheme to marry her off to a rich Genovese merchant; Savonarola's forces conduct the infamous "Bonfire of the Vanities".

After the French king occupies a deserted Milan, he tasks Cesare with killing Ludivico, and Lucretia becomes involved in Neapolitan palace intrigue.