The articleexamines a number of urgent problems of spatial development of seven regional centers of Siberia (cities of Abakan, Gorno- Altaysk, Kemerovo, Kyzyl, Tomsk, Ulan-Ude, Chita) based on data of the Russian state statistics and the results of sociological research conducted in 2021 by the staff of the Department of Geo-Urban Studies and Spatial Demography of the Institute for Demographic Research (IDR FCTAS RAS). The aim of the study was to identify socio-economic and demographic conditions for the development of the centers of the regions of Siberia as nodes of the supporting framework of the country's settlement. Questionnaire data from seven regional centers were analyzed using statistical methods, methods of comparative analysis, as well as graphical and cartographic presentation.The authors identified demographic trends in the development of agglomerations of regional centers of the regions of Western and Eastern Siberia. The territories with a greater degree of regionalization of business revealed a more active involvement of industrial enterprises in the implementation of social and economic development projects. The article evaluates development dynamics of small and medium-sized businesses in the centers of the regions, as well as of higher and secondary vocational education. It reveals general patterns and individual features in the socio-economic development of the centers of the territories under consideration.The article conducts ranking of cities by the degree of influence of negative factors on their development, analyses subjective assessments of respondents of problems of cities of residence with attitudes to emigration. The most vulnerable to depopulation regions, in terms of their geographical location (remote regions of Eastern Siberia), as well as the cities – large centers of high-tech engineering were identified. The paper proposes organizational and economic solutions to overcome these negative factors. The results of the study, according to the authors, can be used to formulate priority measures of regional and economic policy of Siberia and develop its spatial potential.