The social challenges of modern globalization caused by the COVID-19 pandemic have led to significant changes in the development of economic systems at various levels. Social development in the direction of a post-industrial society activates the introduction of digital technologies in all areas of life, which requires paying attention not only to the innovative component of its development, but also to the intellectual one, since the digital transformation requires a constant updating of knowledge; this determines the purpose of this scientific study. The article aims to highlight the influence of intellectual and innovative determinants in the development of regions under current conditions, which are outlined by the manifestations of the COVID-19 pandemic and global digitalization in the development of economic systems. The foundation of the system approach methodology made it possible to distinguish the development trends of the regions in the conditions of the COVID-19 pandemic and global digitalization. It is proposed to create guidelines for the intellectual and innovative promotion, determinants of the development of the regions in the conditions of the COVID-19 pandemic and global digitalization, according to the socioeconomic, scientific-technological, organizational and legal components. The main guidelines of efforts to increase the role of intellectual and innovative determinants in the development of regional systems in the conditions of the COVID-19 pandemic and global digitalization have been tested, taking into account the principles of complexity, integrity, flexibility, efficiency and long term.