Cooperation in research, development and innovation (RD&I) between universities or research institutes and industries plays a fundamental role in the economic development of a country. Industry benefits from state-of-the-art laboratories and technologies from academia, while institutes learn about business reality and market needs. Numerous barriers to the establishment and maintenance of these partnerships have been investigated and reported in the literature, but the information generated by these empirical studies is very fragmented and there is a need to consider the barriers systematically in order to clarify the topic. The aims of this systematic review were to analyze university-industry collaborations set up for the purpose of RD&I in an effort to recognize the barriers and facilitators of the process and to identify the approaches by which such barriers may be overcome. Following searches of the Scopus database and application of the exclusion criteria, 86 relevant articles were identified and submitted to bibliometric analysis. Subsequently, 75 articles were selected for in-depth content analysis, and the ideas embodied therein were presented in a structured and comprehensive manner. Barriers were evaluated according to three different theoretical perspectives, namely the triple helix and the entrepreneurial university, the relational social capital and value creation, and technology transfer and cultural differences. The facilitators were categorized as internal and external. The results obtained highlight the importance of fostering relational social capital and providing tax incentives to facilitate industry's pursuit of innovation through academia partnerships, and also show that collaborative barriers in RD&I may be overcome to some extent by starting with smaller projects and gradually increasing their complexity. Based on the findings outlined in this review, we propose various lines for future research.