Innovative development of the region in the context of global environmental challenges involves the selection and implementation of priorities aimed at the future. In the context of the fourth industrial revolution and the trajectory of development of socio-economic systems with an emphasis on digitalization, the role of technologies is increasing and at the same time the model of their origin and development is changing. The ability to predict emerging technological opportunities and use the potential of breakthrough technologies in a timely manner will allow to plan the innovative development of the territory effectively and systematically, providing it with significant competitive advantages. It is the competitive advantages that make it possible to build strategies for long-term innovative development of the territory, taking into account its uniqueness. In this context, embedding future research in the practice of regional strategic planning is an urgent task. The purpose of the research is to develop a methodological approach to the formation of key competencies in the region in the format of solving the problem of choosing priorities for innovative development of the territory based on the principles of “smart specialization”. Using general scientific and special methods of scientific search, the authors studied the main approaches to the process of forming a strategy for innovative development of the region in Russian and foreign scientific literature, as well as European practice. It is established that the comparative (distinctive) advantages of a region as a basis for its innovative development can be determined by key technological competencies. The paper considers a set of definitions necessary for this purpose. The proposed map of key technological competencies of the region allows to represent and describe the regional “competence” profile clearly, involving the main groups of stakeholders in the innovation process: state authorities, business community, civil society, science and education, according to the model of the four-stage innovation spiral. The authors present a comprehensive technology for organizing entrepreneurial search for regional innovative development as an important issue of using the concept of “smart specialization”, taking into account the national specifics and European experience. In turn, a regional foresight is proposed as a tool for selecting and justifying the priorities of innovative development of the region in the mode of constructive dialogue between the main groups of stakeholders.