Construction resumed when the island passed to Carlo’s sons, Cardinal Giberto III (1615–1672) and Vitaliano VI (1620–1690); the latter in particular, with the financial backing of his elder brother, entrusted the completion of the works to the Milanese architect Carlo Fontana and turned the villa into a place of sumptuous parties and theatrical events for the nobility of Europe.

The island achieved its highest level of social success during the period of Giberto V Borromeo (1751–1837) when guests included Edward Gibbon, Napoleon and his wife Joséphine de Beauharnais, and Caroline of Brunswick, the Princess of Wales.

It is said that Caroline, having fallen in love with the place, did her best to convince the Borromeo family to sell her Isola Madre or the Castelli di Cannero islands; her request being turned down, she established herself on the banks of Lake Como at Cernobbio in the Villa d’Este.

A conference of high representatives of Italy, France, and the United Kingdom was held in the palace at Isola Bella in April 1935, resulting in the agreement known as the Stresa Front.

Isola Bella is a popular tourist attraction, with a regular ferry service from Stresa, Laveno, Pallanza, and Intra.