Literature on science and technology parks (STPs) lacks a systematic understanding of how regional contextual factors affect the performance of STPs. Most studies focus on park-internal factors and neglect the regional context and connections when evaluating STPs’ performance. This paper provides new insight on the role of regional factors for STPs by combining and discussing existing studies on STP performance with literature on regional innovation systems. We conduct an exploratory, systematic literature review of 64 papers that refer to park-external factors in their studies of STP performance. We identify five regional factors (university and research institutes, industrial structure, institutional settings, financial support and urbanization) and assess how these factors have been shown to play a role for STP performance in previous studies. Based on this review, the paper develops a comprehensive framework of how regional contextual factors influence the performance of STPs, which can be used in designing and/or improving STP-performance while taking regional characteristics and needs into consideration. We believe a dynamic and comprehensive understanding of these regional connections can help improve designs of STPs, and thereby their performance.