Messina 1347 takes place during the introduction of the plague epidemic (also known as the "Black Death") and the spread of the infection through the city. During this period, merchant ships delivering luxury goods to Europe brought an unprecedented epidemic to these countries - and one of the first cities affected was Messina, Italy.

In the game, players take on the role of important Messina families who leave the city and move to the countryside for fear of being infected by the plague. As they do this, they focus on saving other residents and helping combat the plague infection in the city. They must also try to thrive in their rural hometown, where they temporarily host rescued residents. They all wait there until the epidemic is over, and then return to Messina to take over and dominate certain neighborhoods of the city.

The Games Friends: "Messina 1347 is once again a masterpiece by Vladimír Suchý. The theme is well implemented and there is a high replayability because the tiles are positioned differently each time. In our opinion, together with Praga Caput Regni and Underwater Cities, this is one of their n best games!"