The concept of Regional Innovation System (RIS) builds upon an integrated perspective of innovation, acknowledging the contribution of knowledge production subsystem, regulatory context and enterprises to a region’s innovative performance. Science and Technology parks can act as a platform to the production of knowledge and its transfer to the economy in the form of spin-offs or simple knowledge spillovers, enhanced by the co-location of R&D university centers and high technology enterprises on site. Although reflecting mainly a science push perspective, they may constitute central nodes in an infrastructural system of competitiveness that articulates other entrepreneurial location sites and bridges Universities to the economy in a more efficient and effective way, being crucial to increasing technology transfer and interchange speed, promoting the technological upgrading of the regional economy. In this paper we discuss the importance of Science and Technology Parks in the building up of a Regional Innovation System, promoting the technological intensification of the economy, a more effective knowledge transfer and sharing and the construction of competitive advantages, with particular importance in follower regions facing structural deficiencies. We oppose to the predominant closed paradigm, which understands science parks’ role in a narrow and “enclavist”, arguing in favor of an open and “integrative” paradigm where the interconnection to other infrastructures and agents boosts the park’s performance and upgrades the regional economies competitiveness infra-structures and innovation capability. We further stress the importance of science parks in signaling capabilities and hence attracting R&D external initiatives, namely, R&D FDI.