The application of a multi-scale approach to the study of socio-economic processes makes it possible to see the importance of large (first, second and third in terms of population in their regions) cities for the formation of a territorial production system of supra-regional education as a whole. In this paper, based on data on the population and the value of the manufacturing industry of large cities of the Volga-Ural macroregion, their dynamics in the period 2005–2021 was traced.Theoretical analysis.The necessity of analyzing the existing territorial structures of the economy at the supra-regional level (macroregion level) is substantiated. The change in the contribution of the largest cities of the VolgaUral macro-region to the population and output of the manufacturing industry of the regions is traced, on the basis of which a typology of cities by the nature of their influence on the socio-economic space is made. Based on the gravitational approach, the potential of the industrial interaction field withinthemacroregion is shown. The problems of its broken configuration are discussed, as well as regional differences in output by industry. Conclusion The analysis made it possible to identify the comparative dynamics of the socio-economic development of large cities of the Volga-Ural macroregion over a fairly long period and typologize it. The analysis showed the isolated nature of the individual cores of the territorial production system within the macroregion, as well as the need for industrial policy for a positive transformation of the system.