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The role of actor connectivity within knowledge clusters, specifically across geographic areas, remains understudied. In this paper, we attempt to advance our understanding of the global system of innovation by evaluating the role of cross-location linkages. We analyse the evolution of knowledge-intensive development processes in Italy, incorporating the dual-direction of knowledge flows, from the national system to the global system and vice versa. We also assess the relative importance of the organization-based and individual-based connectivity. Our findings illustrate how connectivity with the global innovation network reinforces the central role of knowledge clusters as centers of innovation and entrepreneurship.