The goal of the work is to analyze the essence of socio-economic environment of entrepreneurship and prospects for the interaction of socio-economic environment of entrepreneurship and business entities using the example of the North-Western region of Russia. To achieve this goal, the method of statistical analysis was used to determine the dynamics of entrepreneurship development in the North-Western Federal District. The method of expert survey was used to identify priority areas for improvement of external business sustainability of small and medium-sized enterprises at the regional level. The article justifies the relevance of the study of the socio-economic environment of entrepreneurship. The authors consider various scientific approaches to determining the nature and importance of business environment, which is understood as a set of conditions and factors that influence the business sector and become the basis for entrepreneurs’ actions on the development of their activity. The article provides statistical data characterizing the dynamics of the development of the business sector in the territory of the North-Western Federal District. It determines priority areas to increase small and medium-sized enterprises’ external business sustainability at the regional level based on the institutional infrastructure of risk prevention and analyzes the effective infrastructure for support of the business activity.