Italian Wars of 1499–1504 in the context of Italian War of 1494–1498

The Kingdom of Naples, officially the Kingdom of Sicily, was a state that ruled the part of the Italian Peninsula south of the Papal States between 1282 and 1816. It was established by the War of the Sicilian Vespers (1282–1302). Until then, the island of Sicily and southern Italy had constituted the "Kingdom of Sicily". When the island of Sicily revolted and was conquered by the Crown of Aragon, it become a separate kingdom also called the Kingdom of Sicily. This left the Neapolitan mainland in the possession of Charles of Anjou who continued to use the name "Kingdom of Sicily". Later, two competing lines of the Angevin family competed for the Kingdom of Naples in the late 14th century, which resulted in the murder of Joanna I at the hands of her successor, Charles III of Naples. Charles' daughter Joanna II adopted King Alfonso V of Aragon as heir, who would then unite Naples into his Aragonese dominions in 1442.

As part of the Italian Wars, France briefly ruled the territory in 1494 and at the beginning of the 16th century; it then went to war with Spain over the kingdom in 1502, a conflict that ended in a victory for Ferdinand II, who was in full control of the kingdom by 1504. The Spanish held control of Naples throughout the 17th century where it remained an important source of economic and military power for the Spanish Crown. After the War of the Spanish Succession in the early 18th century, the possession of the kingdom again changed hands; the 1714 Treaty of Rastatt saw Naples given to Charles VI of the Austrian Habsburgs. However, Naples and Sicily were conquered by Charles, Duke of Parma (of the Spanish Bourbons) during the War of the Polish Succession in 1734, he was then installed as King of Naples and Sicily from 1735. In 1816, Naples formally unified with the island of Sicily to form the Kingdom of the Two Sicilies.

The Portrait of Isabella d'Este is a drawing (and possible painting) by Leonardo da Vinci which was executed between 1499 and 1500. It depicts Isabella d'Este, Marchioness of Mantua. During the Italian Wars of 1499–1504, the French invaded Italy which caused Leonardo to flee from Milan to Mantua. There he had met Isabella, where she commissioned her portrait from him. Whether Leonardo completed the portrait is unknown. There is evidence through letters of the time that he held a fully completed painting of her, but they are vague in describing it. It is possible that the painting was lost to time or that it was, in fact, never completed at all. A version of the portrait in oils on canvas was found in a collection in Switzerland in 2015, but it has yet to be verified.