The monograph presents the results of a comprehensive study of the state, potential, forms, challenges, weaknesses and opportunities for deepening cooperation between research organizations, universities and enterprises in Bulgaria carried out within the research program of the Economic Research Institute at BAS and ended in 2020. The investigation is based on empirical analysis of information from official statistical national and international databases and reports of international institutions, and of quantitative, qualitative and expert assessments of the “research-business” interaction in the country. The study applied its own approach to determine a set of indicators characterising the cooperation between academia and business in the creation and implementation of new knowledge, products and services. As a result of the research, assessments are made of: the stages of the evolution of European initiatives aimed at strengthening cooperation between science, higher education and industry; the process of establishment of the national normative and institutional framework for ensuring the interaction between the academic sphere and the business, and the practical results of its implementation; the potential and needs of the business sector for cooperation with the academic sphere in the field of research, education and innovation; the potential of the academic sphere to create and transfer new knowledge and to educate specialists with professional knowledge and skills necessary for the business; Bulgaria’s position on innovation and competitiveness in the EU through the prism of the studied relationship, highlighting a significant lag behind the EU average and most other member states. Types and forms of cooperation between the two spheres are systematised and practices of their implementation in the country are derived. Conclusions are formulated about the state of the relationship “academic sphere - business” and more important challenges for its development are identified. A low degree of connection and interaction between the two spheres is found. The main groups of problems for establishing and developing the cooperation between the academic sphere and the business are systematised, and in each of them existing weaknesses and barriers for the interaction between the two spheres are identified. Areas for its improvement and expansion are defined and specific development opportunities are formulated and proposed. The monograph is intended for line ministries, departments and other competent bodies defining Bulgaria’s policies in the fields of higher education, science and innovation, governing bodies of universities and research institutions, employers’ and non-governmental organisations, as well as for scientists, lecturers and other actors that may be concerned.