This paper aims to reveal the role played by open innovation schemes in the development of new competitive advantages. Furthermore, it aims to present a normative model for networking knowledge clusters, that is, traditional clusters that are applied to the case of the Cova da Beira region (Portugal) such as Agro-Food, Textile, and Public Sector; and a set of emergent clusters that include Bioscience, Biotechnology, Multimedia, Tourism, Health, and Knowledge. In this paper, the basic framework about clusters was expanded, taking as reference the studies of Porter (1985, 1990, 1998, 2005), Feldman (1994), Porter and Stern (2001), and Furman, Porter and Stern (2002). The problematic related to open innovation schemes is integrated in this framework in order to reveal the importance of building new kinds of open innovation networks that don’t involve the geographic concentration of the enterprises. After making a literature review in order to present the analytical framework that includes the clusters theory, a normative model is presented through the development of a case study applied to the Cova da Beira region (Portugal). This option is due to the existence of a local University that has historically interfaced the launching of open-innovation spin-offs into local and international clusters networks. The present paper reveals a high degree of originality, since it contributes to the introduction of the concept of open innovation into the literature about clusters. The main point is that open innovation provides two main implications to build up and leverage both internal and external knowledge into international clusters networks. First, this study presents a basic implication for several agents such as, entrepreneurs, researchers, and policy makers; that is, universities are principals in interfacing the sources of open innovation and the transfer of processes of knowledge into the international clusters networks. Second, it promotes the inclusion of the issue related to the creation of international and institutional networks in the short agenda of the referred agents in order to promote the introduction of new open innovation schemes.