Russia’s transition to innovative development is required to ensure the sustainable competitive growth. At the same time, the share of the high-tech sector in innovation costs today is about 15 %. The study suggests ways to improve the system of innovation management in Russian regions. Analysis of modern theories on the organisation of regional innovation processes confirmed a hypothesis that innovation management should consider the regional innovation ecosystem as one of the key sustainable growth institutions. A proposed ecosystem approach states that regional innovation ecosystems in the context of globalisation depend on the coordinated goals of socio-economic and innovative development, differentiated approaches to their construction, sustainable flows of knowledge and technology, diversity and competition of participants. The research determined such priority directions of the state policy as the recognition of the lack of alternative to innovative development; creation of conditions for high-tech industries outside the established business structures; increase in budget research and development (R&D) expenditures; strengthening of self-organisation of science; stimulation of horizontal interactions between science and business. The presented differentiated approach to innovative strategies of Russian regions considers their production and technological specialisation, as well as the state of science and higher education. A described methodology for selecting the most promising regions for innovative transformations is based on a comparison of the values of the author’s indices for the development of scientific and educational space and high-tech industries. The calculations show that, in addition to Moscow, Moscow oblast and Saint Petersburg that are already at the centre of the country’s innovation system, regions occupying the first 10–15 positions in the constructed rating (Nizhny Novgorod, Sverdlovsk, Novosibirsk oblasts, Republic of Tatarstan, etc.) can also become local innovation centres. The obtained results can be used in the state innovation management of the constituent entities of the Russian Federation.