The paper highlights the importance of Genoese migration in the manufacturing system of Spanish monarchy during the 18th century by focusing on the port of Cadiz, which was the main hub of the Spanish colonial trade, and the city of Buenos Aires, on the monarchy’s southern frontier. The Genoese migration found favourable conditions towards its settlement in Spain. In the Andalusian region in particular, the Genoese not only maintained a role in trade intermediation, but were also at the core of the local production of manufactures for the Spanish and American consumption. The Spanish institutions fostered immigration of foreigners who practiced a craftsman or mechanic profession. During the eighteenth century, the reforms aimed at strengthening the Spanish industry in Cadiz offered new prospects to the craftsmen specialized in the production of paper, silk textiles, and ships, while the Crown’s policy encouraged Genoese businessmen to relocate their production plants to Spain. In Buenos Aires, on the contrary, the case of the shoemaker’s guild’s failure helps to explain how the Spanish mercantilist policies and the characteristics of the local market impeded the foreigners to play a significant role in local manufacturing until the wars for emancipation.