The main directions of the regional economy advanced development include the stimulation of small and medium business, import substitution policy, improvement of the professional qualities of the economically active population, and development of a favorable environment in the interaction of business and government. However, in modern conditions, a new driver of economic growth is needed: the digital transformation. For successful transformations, resulting in a significant increase of efficiency, clearly defined goals and business objectives are required, i.e., the available strategy, implementation of which is realized in the need to achieve a specific state of the economic system, in which its development is ensured through synchronization with national, regional and sectoral priorities. Moreover, along with the preparedness to strategizing, an appropriate external environment is essential, presuming the capabilities of the regional economic system to support innovation. The article presents the authors’ approach to the problems of analyzing the processes underlying the regional economy. A purposely designed toolkit consisting of economic and mathematical models, databases, and applied software is aimed to intensify the framework of studying the regional economy development management. The example of the socio-economic system of St. Petersburg enabled to carry out a comprehensive assessment of the consistency of the regional economy in the formation of a favorable business environment for economic entities at the initial stage of digital transformation. The result of the study is the substantiation of the provisions that to reduce the risks of stagnation in economic growth, support of the leading regional enterprises is essential, which act as the leaders of progress, introducing capital-intensive technologies, and conducting digital business transformation. Availability of such poles of growth reduces the barrier in terms of accessing digital technologies for small and medium businesses, thereby ensuring the sustainability and competitiveness of the region as a whole. The paper made it clear that the key to the successful digital transformation is the creation of IT ecosystems that implement the concept of a systematic approach to decision-making in business management, applying knowledge economy technologies, such as predictive analytics, artificial intelligence, big data, cloud computing, etc. Recommendations for the generating of unified information space in the concept of a digital enterprise are provided.