Cesare loses his lover and his daughter, leading to a painful defeat, and Lucrezia's betrothal becomes politically and emotionally complex.

Cesare's renegade generals mount a rebellion against him, while those close to Rodrigo conspire against him, all on the eve of Lucrezia's wedding.

Lucrezia meets her new family with mixed results, while at home a malaria outbreak has historic consequences for the Borgias.