Identifying the spatial structures of economic activity within a supra-regional entity is an urgent scientific task. In this study, it is solved using a combination of a framework approach and a model analog of the gravitational interaction for the cities of the Volga-Ural macroregion. According to the cost of industrial production of cities with a population of more than 100 thousand inhabitants (i.e., the first and second cities of their regions) and the distance between them, an industrial-urbanized framework of the macroregion was built, demonstrating the potential of economic ties within it. The analysis of the strength of ties allowed us to identify the peripheral and central cities-industrial centers. Among the first ones there are the cities of Orenburg and Penza regions, among the second ones – Ufa, Samara and Tolyatti. In addition, the functions of the second cities of the regions were analyzed and the degree of industrial orientation of the first and second cities of the macroregion was revealed.