The region of Calabria, already at the Union of Italy in 1861, and even more so at the institution of the Republic (1948), was among the poorest and most marginal regions not only of Italy but also of the European Union. Despite the numerous funding policies active to de‐marginalize the area at both the national and European scale currently, mainly European Regional Development Fund (ERDF) and European Social Fund (ESF); up until 1992 mostly the Extraordinary Intervention for the Mezzogiorno, there has not been a significant improvement or change in this tendency. In this paper, through a processual approach based on historical and geographical literature, I examine the position of the administrative framework of the region as a possible codetermining factor of such a condition of peripheralization, trying to assess whether and how a careful reform of it could improve the potential of current de‐marginalization policies. Ultimately, starting with the reconstruction of the numerous factors leading to Calabria's marginality, this study highlights the dynamic and relevant role of the framework in a perspective of the development and valorization of the area.