The presented study proposes approaches to assessing the performance of small, medium, and large regional enterprises in the Russian Federation based on developing a system of indicators and calculating a cumulative index of strategic stability of enterprises. Aim. The study aims to develop methodological approaches to assessing the impact of entrepreneurial activity on the development of a region that is a constituent entity of the Russian Federation. Tasks. The authors identify the specific aspects of development of the complex of enterprises, including small, medium, and large enterprises, as the crucial growth factor for the depressive regions of Russia and propose a methodology for calculating a cumulative index for assessing the performance of enterprises - the index of strategic stability of regional enterprises. The authors also identify potential areas of application of the proposed approaches to the analysis of enterprise performance for the purposes of regulating regional development and determining strategic directions for the spatial development of Russia. Methods. This study uses general scientific methods of cognition, such as analysis, synthesis, comparative and statistical analysis, systematization, and cumulative index calculation to propose methodological approaches that would make it possible to compare regions in terms of the efficiency of enterprise development and the impact of enterprises on regional economic development, and to identify directions for improving the strategic stability of enterprises in depressive regions. Results. The study shows that depressive regions have a lower share of large enterprises, lower innovative activity of enterprises, less favorable demographic processes among employees, significantly lower share and rate of growth of profit tax in the total taxes of the region, etc. The complex of enterprises in depressive regions is not strategically stable. Conclusion. Regions can be compared in terms of strategic stability using a cumulative index - the index of strategic stability of regional enterprises, which comprises six subindices. Preliminary calculation of indicators included in the cumulative index, as shown through the example of the Pskov and Ivanovo regions, makes it possible to identify the specific aspects of development of small, medium, and large enterprises in depressive regions, to specify the definition of “strategic stability of regional enterprises”, and to propose directions for improving the strategic stability of enterprises in depressive regions using the results of application of the proposed methodological approaches.