The territorial agglomeration of interdependent enterprises has a positive influence on the competitiveness, the performance and the development of national economies. This is a widely accepted intuition in economic theory, and it dates back to the works of Alfred Marshall. In particular, these phenomena have been depicted through the theoretical framework of the “Industrial Districts”. Another significant impulse to the debate was provided by the GREMI (Groupe de Recherche Européen sur les Milieux Innovateurs), through the concept of milieu innovateur. Later, Michael Porter’s studies and dissemination works granted great visibility to the dynamics of agglomeration of industries, which since then are better known among policy makers as “clusters”. At any rate, the importance of the cultural element in the concepts of “cluster”, milieu, and “district” is undeniable. This is evident also when observing the phenomenon from a historical perspective. Evidence shows that the strength of a local economic system, and its capacity to grow and to innovate, are closely related to the pattern of knowledge (thus cultural) stratification, to the territory itself and to learning capacity. Moreover, one can observe that cultural socio-economic elements are embedded in technology, thus they play a key role when considering the dynamics of innovation process and growth opportunities for Small and Medium Enterprises (SMEs). With this respect, the paper will present some relevant case studies of technical assistance carried out by in the field of industrial cooperation with several non-EU Mediterranean countries. In particular, the paper will present those case studies where initiatives were set up with a view to encourage cluster dynamics in regions (i.e. Aleppo, Syria or Yazd, Iran), where the main sector of activity (textile and clothing industry) is historically and culturally based. In particular, several factors were involved, such as the cohesion of stakeholders for the creation of innovation, the development of new products, and the competitive advantages for the local productive system. The project approach and its conclusions confirm the fundamental role of culture and culture-based activities in the process of economic development, especially when considering SMEs, where culture represents both an embedded strategic foundation for the creation of cluster dynamics, and a significant potential for their future development affecting innovation trajectories.