After being poisoned, Pope Alexander fights for his life unaware that the cardinals are plotting on his deathbed.
Having gained the evidence needed, Alexander banishes all of the cardinals that he doesn't trust as Lucrezia finds herself annoyed with her future in-laws.
The dismissed Cardinals are stripped of the wealth and titles as the Vatican Treasury is set ablaze by Cardinal Versucci.
Cardinal Farnese in his new role discovers the theft as Venice puts in a request for help after pirates invade.
Cesare finds an ally in the form of Archbishop d’Amboise, Charlotte d’Albert as tragedy strikes as Bianca commits suicide.
With the French army as backup, Cesare lands in Italy as Alexander is concerned about the lack of funds needed.
In an attempt to contain the virus, Cesare has the palace burnt as Lucrezia blackmails a prince to help claim the throne for her husband.
Caterina Sforza plans to ruin the festival whilst plotting to have Cesare murdered at the same time.
Brother and sister are reunited when Cesare manages to rescue Lucrezia but Alfonso starts to have suspicions.
Using the army, Cesare makes do with Juan's original intentions as Caterina Sforza attempts to kill herself.