Currently, the regulation of investment flows is an integral part of managing the socio-economic development of the region. At the same time, the investment potential of any Russian region is determined by the effectiveness of the implementation by regional territorial authorities of their social, economic, environmental policies for the development of the Russian region. The analysis of investment opportunities of Russian regions is one of the tools of the monitoring component of the mechanism for managing the investment potential of the studied Russian regions of the Southern Federal District. In this regard, one of the most urgent problems of managing sustainable socio-economic development of the studied Russian regions is the problem of assessing the sustainability of the investment potential of the regions of the analyzed macro-region. The purpose of this publication is to consider the problems of forming a regional mechanism for managing the totality of investment resources of the Southern Federal District. Methodological approaches to the analysis of investment opportunities of Russian regions and the analysis of the criterion indicator of the sustainability of the potential of investment resources of the regions of the analyzed macro-region have been studied. In order to achieve the goal, the problems of formation and functioning of the mechanism for managing the regional potential of investment resources, the analysis of regional investment opportunities and the criterion for the stability of the investment potential of the analyzed regions of the macro region and methods of its calculation have been analyzed. The methodological basis of the study includes a systematic method, methods of statistical analysis, expert methods. The theoretical and methodological basis of the study was the work of domestic and foreign authors in the field of assessing the investment potential of the region, its management. The result of the conducted research is a methodology for assessing the criterion of sustainability of the potential of investment resources of the Russian regions of the studied federal district. The proposed methodology allows regional authorities to assess the sustainability of the potential of investment resources of the Russian regions of the Southern Federal District, to predict the amount of investments in fixed assets of economic entities of the analyzed regions, their labor, financial, innovation, production, infrastructure, consumer potential. In particular, the proposed methodological approach makes it possible to form a system of measures to increase the potential of investment resources, both in the regions of the Southern Federal District of Russia in particular, and in the Federal District as a whole.