The spatial development of the region ensures the stability of the entire socioeconomic system in the long term, determining its resistance to the effects of external shocks, increasing the ability of the regional economy to recover from these shocks. This explains the increased interest in finding solutions to the problems of a sustainable spatial development of Russian regions in modern conditions. According to the provisions of strategic management, the sustainability of economic systems, in turn, depends on internal factors: on the economic structure and features of development, on the quality of institutions, on the balance of development of economic, on social and environmental factors of the functioning of society under existing resource constraints. The stability of the region's economy largely depends on its ability to withstand the influence of negative factors in times of crisis. At the same time, despite the theory of cyclical economic crises, each of them has its own nature and form of manifestation. The stability of the spatial development of the region is a function of the factors of its instability. Therefore, special attention must be paid to factors that increase instability and reduce the stability of the region's economy, turning its relatively stable system into an unstable one, unable to ensure the unity of socioeconomic, institutional, and environmental development. During this period, there is a reduction in the resource potential of the region, which is unable to meet the vital needs of people living in the region, to create zones of their favorable residence in these territories. The group of internal factors of instability should include, first of all, the decline in production in the region, the growth of inflation, the outflow of the population, weak entrepreneurial and investment activity, the reduction in effective demand, monopoly, etc. The factors of the instability of the economy of the regions are, first of all, external ones, since in the modern conditions of globalization the spatial development of each region is characterized by an increasing strengthening of interdependencies at the interstate, national, and regional levels, manifested primarily in the transformation and restructuring of the economy, strengthening of international institutions of influence, homogenization and convergence of economic and social relations. Modern realities necessitate the improvement of appropriate protective anti-shock mechanisms that ensure the economic sustainability of the development of the socioeconomic space of the regions and the Russian Federation as a whole. The aim of this study involves consideration of new challenges to the sustainability of the spatial development of the region, which is considered on the example of Perm Krai.