She was also the niece and heir of childless Giovanni Antonio Orsini del Balzo, Prince of Taranto.

On 30 May 1444/1445, Isabella married Ferdinand of Aragon, then Duke of Calabria (1423–1494),[2] natural son of Alfonso V of Aragon who had recently conquered the Neapolitan kingdom from French Angevins, and thus was the new liege lord of Isabella and her family.

Also, Alfonso wanted his loyal people (such as his own son) to have feudal fiefs in his new kingdom, which would happen in the future as soon as Ferdinand and Isabella succeeded in Taranto.

Queen Isabella died on 30 March 1465, and was buried in San Pietro Martire.

Her heir was her eldest son, the future King Alfonso II of Naples.