BACKGROUND: This article is devoted to the study and improvement of theoretical approaches to the formation of the neo-industrialization paradigm as the basis of the innovative trajectory of the development of economic systems. The relevance of this study is due to the growing importance of neo-industrialization policies as an objective basis for the transition of the Russian economy to an innovative type. AIM: The aim of the work is the theoretical justification and development of scientific and practical recommendations for the implementation of the innovative trajectory of the development of economic systems in the conditions of neo-industrial challenges. METHODS: We conducted a literature review of relevant scientific publications. We analyzed and synthesized theoretical concepts. This way, we pointed out the conceptual foundations of the formation of the neo-industrialization paradigm. Using the inductive method, parameters and principles of Russian industry innovative development before and during the coronavirus disease pandemic are define. We used Rosstat data of innovative goods circumference and current innovation expenditures for structural and functional analysis. RESULTS: The analysis is made and the most important parameters of the formation of the neo-industrialization paradigm are identified. Modern trends, critical neo-industrial challenges, and threats to the innovative development of economic systems are structured, refined, and typologized. The most effective instruments of state participation in enhancing innovation processes in the context of neo-industrial challenges have been consolidated. CONCLUSION: A paradigm concept for the innovation of economic systems in the context of the implementation of neo-industrialization policies has been formed as a response to modern challenges and threats.