Recent research on science and technology parks (STPs) has called for including regional contextual factors in studies of STP performance. However, no study has yet systematically assessed how regional contextual factors support or hinder STP performance. We apply a systematic framework to a comparative case study of three regional STPs in Thailand and analyse the effects of varying conditions along five dimensions: urbanisation, industrial structure, regional institutions and culture, university and research institutes, and financial resources in relation to the performance of each STP. The three Thai regions are similar in both size and levels of urbanisation and are governed by the same national programme for STP development, which provides a good methodological set-up for analysing the effects of varying regional contexts. Findings reveal that positive STP development is grounded in the presence of an innovative culture in regions driven by an active collaboration among local actors. Moreover, despite STPs being located in the same national innovation system, different regional contextual factors result in different levels of STP performance. A holistic understanding of these regional connections can help improve designs of STPs, and other supportive policies that are important for regional innovation development.