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Although it is generally anticipated that innovation as such leads to regional prosperity (Asheim et al. 2011) there is lack of empirical evidence that confirms the direct linkage between the innovation capabilities of regions and welfare increase. It is suggested that entrepreneurship can be seen as a missing link that helps to transfer innovations into business outcomes (Braun et al. 2012). The aim of this explorative paper is to create the holistic view of the regional development, its innovation system related to cleantech, entrepreneurship and triple helix collaboration on the example of Øresund, Danish-Swedish transnational region. Eighteen interviews with regional stakeholders related to academia, business and administrations were conducted in order to understand their vision on cleantech innovation and entrepreneurship development. In addition, available secondary data such as peer-reviewed articles, industry and governmental reports were analyzed. It was found that the process of interregional collaboration and networking for the development of research-based innovations in Øresund seems not as promising as it was expected. Our findings reveal that in order to innovations in cleantech to be utilized, the efforts of entrepreneurs are necessary to promote knowledge spillover from research institutes and “locked” systems into business environment. Upcoming economic recession, could stimulate the development of entrepreneurship, and academic entrepreneurship in particular. Increasing development of research-based innovations related to social science significantly extends the magnitude and possibility to involve academia and students in academic entrepreneurship and cleantech. It was concluded that new agenda for the interregional development could be associated with cleantech. Some of the measures that could support cleantech development include: redirection of public funds towards cleantech, development of sociotechnical innovations; cooperation between cleantech startups with non-cleantech industry, development of fiscal incentives and tax breaks as well as promotion of small and medium cleantech enterprises