The issue of resilience of regions is considered in the context of the conditions for ensuring the possibility of its further development under the influence of destructive external or internal factors. It has been substantiated that a possible solution to the problem of determining the sustainability potential should be based on a comprehensive analysis of existing natural, social, economic, and political factors. To assess the resilience of regions, it is proposed to assign them to groups, which are further defined as “domains of influence”. It is proposed to consider the interaction of domains as the main characteristic of the system in the process of its response and adaptation to external influences. To analyze and determine quantitative indicators of this process, it is proposed to use the concept of interaction of ”domains of influence” in the “circle of sustainability”, according to which the condition of balance between the values of domain indicators will characterize the degree of resilience of the region.