The game Princes of the Renaissance is set in Renaissance Italy. Player takes on the role of one of the minor Condottiere princes, such as the Gonzagas or d'Estes. Then there are the five big major cities: Venice, Milan, Florence, Rome, and Naples. These are not controlled by individual players, but players gain 'interests' in them as the game progresses. Each of the major cities has six tiles, most of which represent a famous character such as Lucrezia Borgia or Lorenzo Medici. Each tile has its own special properties linked to the character on the tile. Thus Cesare Borgia will help you become more treacherous, while a Venetian merchant will help to increase your income. These tiles are also worth victory points, depending on the status of the city when the game ends

A city's status will change as a result of conflict. When two cities fight, they each need a Condottiere to fight for them. Players bid, using influence points, to determine who will represent each city. The outcome of the war depends on a little luck and the size of each player's army. Each player also gets paid for fighting, regardless of the outcome of the war. Thus players can convert influence into gold, which in turn can be used to buy more City tiles.

No game on the Italian Renaissance would be complete without some element of treachery. Players can be openly treacherous by buying Treachery tiles, which will allow them to do nasty things like steal influence, bribe troops, or knock other players out of an auction. However, the game also allows players to be devious in other ways, that still remain legal. Making sure that a war goes the way you want is an important part of the game, and it is not always the player with the best army who ends up fighting. Want a city to lose, become Condottiere for them and make sure you have a really bad army, or use Treachery tiles to bribe your own troops not to fight. At some point a player will become the Pope, which means he can form a Holy League (i.e. join one side in a battle). Want to make sure the Pope is on the 'right' side, why not bribe him? What each player negotiate over is up to them. The game does not require negotiation and works perfectly well without it, but it remains an avenue for players to explore.