In the modern Russian space, the socio-economic role of the regions is increasing. The region, first, is part of the system of a federal state, and second, it is a relatively independent economic system that has its own political, economic, social and cultural characteristics. Analyzing the essence of economic federalism from the perspective of various branches of economic science will allow a more systematic study of federal and regional development interests. Therefore, the purpose of this article was to identify the specific features of economic federalism from the standpoint of regional economic science. Comparative analysis was used as the research method. It was found that economic federalism, from the standpoint of regional economics, represented a system of relationships and a mechanism for interaction between the central core and the territories of the country regarding the provision of economic resources for state functions at different levels of government. The formation of an effective model of economic federalism should be based on the organization of interactions between the federal center and the regions, and not on strengthening the ‘power vertical’, which will allow combining the interests of the federation with the interests of its subjects and municipalities, ensuring the sustainability of territorial development. Keywords: economic federalism, regional economy, mesoeconomics, territorial development