Foreign Domination - The Spanish and French
The solemn intentions declared at the Peace of Lody only lasted a short time. Scarcely ten years later the Sforzas took over Genoa (1464), which had become a pale reflection of the once glorious republic and the energetic rule of Simone Boccanegra (1339-63, with a gap between 1344 and 1356) and now gravitated towards French influence. Plots and disagreements underlined some of the best-established signorie, such as the Sforza and Medici, fostered by papal interests that in this period were characterized by the most blatant nepotism.

Also in the Kingdom of Naples there occurred conspiracies among the barons, indicating a lack of capacity on the part of various Italian States, despite their now solid economic foundations, to provide a stable political and administrative structure. However, there were already worrying signs of a financial crisis in the bankruptcy of prestigious banking families, like the Bardi and Peruzzi, who were ruined by the insolvency of the sovereigns and princes to whom they had made loans. The whole system being threatened by seigneurial particularism.

Consequently, the great European powers of the period (France, Spain and the German Empire) did not find it difficult to expand in Italy, often using dynastic claims as justification.

Charles VIII of France descended into Italy to claim the throne of Naples (1494-95); his successor Louis XII was a pretender to the Duchy of Milan (1499); there was yet another Franco-Spanish contest over the division of the Kingdom of Naples, secretly agreed at Grenada (1500); cession of the Ticino to the Swiss Confederation (1503); and, finally, there was the French reconquest of Milan (1515) by the Valois Francis I and his subsequent agreement with the Spanish ruler Charles V, at the Peace of Noyon 1516, whereby Italy was to be divided into two spheres of influence, French in the north and Spanish in the south and the islands.

With the Peace of Cateau-Cambrésis 1559, between Henry II of France and Philip II of Spain, the predominance of Spain over Italy was confirmed. This was directly represented by the three kingdoms of Naples, Sicily and Sardinia (1503-1734) governed by a viceroy, by the Stato dei Presidi in Tuscany (1559-1714) and by the Duchy of Milan (1535-1714).
The consequences of this new alignment, also on the cultural and economic level, were not slow to manifest themselves. Though the culture of the Italian Renaissance was to continue for some considerable time to influence the rest of Europe, nevertheless Italy gradually became marginal to the cultural, scientific and political movements of modern Europe.
The opening of the 18th century was marked by important differences among the European powers, which increasingly involved, through rapidly changing alliances, the Italian States. The War of the Spanish Succession (1701-14) was concluded by the treaties of Utrecht (1713) and Rastatt (1714), resulting in Italian territorial changes: the kingdoms of Naples and Sardinia were given to Austria, together with the duchies of Mantua and Milan and the Stato dei Presidi, while Sicily went to Vittorio Amedeo II of Savoy along with the title of king. A couple of years after, in 1718, Sicily was exchanged for Sardinia, thus creating the new title of the state of Savoy.