She was engaged in 1495 at the age of 3 years old to "Ferrante" Fernando Francesco d'Ávalos, son of the marquese di Pescara, at the insistence of Ferdinand, King of Naples.

In Ischia, Colonna received a typical humanist education in literature and the arts from Costanza d'Avalos, the aunt of her betrothed,[4] and gave early proof of a love of letters.

During the months of detention and the long years of campaigning that followed, Colonna and d'Avalos corresponded in the most passionate terms both in prose and verse,[3] but only one poetic 'Epistle' to her husband has survived.

[7] Joseph Gibaldi has noted that Vittoria's poem to Ferrante was a direct imitation of Ovid's Heroides in which famous ancient women such as Dido and Medea address complaints to their absent lovers.

Colonna, who was hastening to tend him, received the news of his death at Viterbo[3] She halted and retreated to the church of San Silvestro in Capite, in Rome, where there was a convent in the Order of Santa Chiara.

Abigail Brundin has suggested Clement and Ascanio's motivations for refusing Colonna's request were that they hoped for a future marriage to create another desirable political alliance.

The Sack of Rome (1527) finally gave the Colonna family the opportunity to improve their relationship with the Medici pope, Clement VII, by offering help to the Roman population.

During his stay on the island, he wrote his unpublished Dialogus de viris ac foeminis aetate nostra florentibus, which is set on Ischia between the end of September and the beginning of December 1527.

[15] In 1537, Colonna was in Ferrara, where she made many friends and helped to establish a Capuchin monastery at the instance of the reforming monk Bernardino Ochino, who later became a Protestant.

[3] At the age of 46, in 1536, she was back in Rome, where she won the esteem of Cardinals Reginald Pole and Contarini and became the object of a passionate friendship on the part of 61-year-old Michelangelo.

[16] Her removal to Orvieto and Viterbo in 1541, on the occasion of her brother's revolt against Paul III, produced no change in their relations, and they continued to visit and correspond as before.