The article deals with the issues of spatial mobility of the population in the regions of the Russian Federation. The relevance of the study is determined by the increasing importance of these processes to ensure the sustainable development of the country as a whole and its individual territories. The aim of the research is the formation of an economic-mathematical model of population migration in the regions of the Russian Federation, taking into account the cumulative impact of multidirectional indicators of socio-economic development. To achieve this goal, a statistical analysis was carried out to identify the correlation between the indicators characterizing the dynamics of migration processes and the socio-economic development of Russian regions. In addition, the methods of structural analysis, analysis of the dynamics, methods of economic and mathematical modeling were used. The conducted clustering allows you to visually see the imbalance of migration processes between the western and eastern parts of the country. Based on the analysis of statistical data, a list of twenty-four indicators (including those characterizing economic development, social security, public finances, demographic situation, etc.) that have a significant impact on migration processes in the regions of Russia was determined. An algorithm for determining the integral indicators, taking into account the degree of «multidirectionality» of particular parameters, is proposed. The proposed approach has been tested on data from the federal districts of the Russian Federation, in particular, a set of regression equations has been developed, describing the relationship between the values of the integral indicators of various spheres of society and the coefficients of migration growth. The scientific novelty of the proposed approach lies in the implementation of a comprehensive interdisciplinary view of the problem under consideration using formalized modeling methods and tools, which allow to quantify possible scenarios for the evolution of socio-economic and demographic processes, calculate their impact on the transformation of the territorial settlement system in the long term. The results can be used to make decisions in the field of demographic policy and management of regional development in the Russian Federation.