1492: The Pope dies. Rodrigo Borgia in spite of his age and his many illegitimate children sees a last chance for election to the Papal throne. He sets about achieving it by a mixture of bribery, blackmail and political cunning.

1495: Charles VIII of France, at the head of a vast army, invades Northern Italy on his way to claim the Kingdom of Naples. Rome stands defenceless in his path. Has the power of the Borgias been shortlived?

Lucrezia awaits the annulment of her marriage and the birth of her baby in a remote convent. Juan is dead. Lucrezia does not know that Cesare arranged the murder. because of a mistaken belief that Juan had made her pregnant.

Cesare has renounced the priesthood for worldly ambition. King Louis of France has given him a Dukedom and a wife. Alfonso Biselli, Lucrezia's new and adored husband, knows too much about Cesare's secret treaty with the French and fears for his life.

Against the Pope's will, Cesare has caused a rift between Rome and the Kingdom of Naples by the assassination of Lucrezia's second husband. While she mourns at Nepi, he has arranged a secret meeting with another enemy of Naples.

Luerezia has been persuaded to agree to another marriage, this time to Alfonso d'Este, eldest son of the Duke of Ferrara; but Cesare, demands that her first loyalty be always to him.

Rodrigo Borgia has lost control of Cesare, who has made as many foes as conquests. As Cesare rides to Milan to meet Louis XII of France, his enemies attempt to join forces against him.

The Pope, fountainhead of all Cesare's power, is dead. Suddenly surrounded by enemies, in need of all his strength and cunning, Cesare lies gravely ill. The power of the family is in jeopardy.

Although Cesare has failed in his attempt to poison his old rival, Cardinal Rovere, he believes he can control the new Pope Pius III. But Pius' reign is rapidly cut short.