A few months after the Pazzi Conspiracy, Lorenzo is still animated by the spirit of revenge. There is a distant clash between Lorenzo and Pope Sixtus IV; the cruel count Riario - the last of the conspirators left alive - tries to take advantage of this conflict. A Dominican friar arrives in Florence who seems capable of reading Lorenzo's heart: Girolamo Savonarola.

The entry into the field of the Kingdom of Naples alongside the papal troops is likely to mark the end of Florence. Among the Priors there are those who doubt Lorenzo, but the Magnificent, determined not to let Florence fall into the hands of his enemies, finds a stratagem to deprive the Priors of authority. Lorenzo decides to leave for Naples to try to break the encirclement and restore peace.

Arriving in Naples with Bernardi, Lorenzo finds it difficult to convince King Ferrante of Aragon to abandon the alliance with the Pope. While the Magnificent tries to win the king's trust, Florence remains under siege: the people and Clarice herself fear that Lorenzo has abandoned them.

Seven years have passed and Lorenzo hopes to close the accounts with the Pope by obtaining the signing of a peace treaty between the various Italian rulers. Riario hopes to induce Lorenzo to return to open war. While the Magnificent faces this new diplomatic crisis, his mother Lucrezia involves Clarice in the management of the bank. Worn out by the constant clash with Sixtus IV, Lorenzo decides to start his son Giovanni on an ecclesiastical career hoping to increase the influence of the Medici in the Roman Curia. The Treaty of Bagnolo, signed by all the Italian rulers, marks the triumph of the Medici family and Lorenzo, who has become the deciding vote of Italian politics.

Sixtus IV is dead. Lorenzo and Clarice travel to Rome to support the election of their candidate for the papal throne, but they have to deal with the plots of Riario. The Medici find an unexpected ally in Caterina Sforza, Riario's wife. Despite the family's efforts, the new Pope Cybo proves difficult to control. In Florence, Savonarola harangues against Lorenzo for his influence in the conclave.

Lorenzo begins to show the first symptoms of a serious illness while his political enemies decide to attack him, questioning the solidity and provenance of Medici Bank's capital. Among these, Tommaso Peruzzi, once a supporter of the family, is now eager to bring to light a scandal that would condemn the Medici to exile. To cover up the crime and avoid losses, the Magnificent risks a new war and plans to kill Peruzzi.

Savonarola, who had taken Tommaso's confession, denounces his killing and openly accuses Lorenzo, who however continues to deny. Clarice begins to suspect the truth. To continue his strategy of control over the Holy See, the Magnificent makes a promise that triggers a family crisis.

Lorenzo allows Bernardi to convince him that the only solution not to lose everything is to kill Savonarola, whose following gets bigger and bigger. By now, the friar openly preaches the overthrow of the established order to found a new Jerusalem. Lorenzo's plan is ready and the assassins recruited ...