A significant part of Russian regions is resource-based and specializes in the extraction and export of natural resources. The paper aims to identify the link between the presence of natural resources in the region and its economic growth, especially in the period of low oil prices. The methodological toolset includes elements of cluster and regression analysis, as well as the method of smart specialization. The allocation of resource regions was carried out through cluster analysis. Regression analysis was applied when establishing the link between the presence of natural resources and indicators of economic development. The justification of priority directions of sustainable economic development of Russian resource regions was performed using the method of smart specialization. It was shown that at least one third of all regions of Russia specialize in the extraction of natural resources. For the majority of resource regions, including the ones specializing in oil and gas, positive relation between the presence of natural resources and economic development was revealed. Most regions have features of mono-industrial. Low level of diversification and connections between sectors in the territory does not allow for complex development through spill-over and multiplicative effect. Finiteness of the natural resource and high dependence of extraction revenues on highly volatile prices and political situation presents an additional challenge for sustainable economic growth. In absence of developed intraregional economy and innovative type of specialisation, this can lead to decreasing production efficiency and lowering economic growth. Directions of innovative development within the framework of smart specialization, based on knowledge and innovation, resource efficient, greener and competitive economy should include processing sector, related and associated industries, such as chemistry, engineering, construction, services, financial sector, IT industry and a number of others.