The development of regional industry, structural changes, industry diversification, and the transition to a new industrial level in modern conditions are limited by the strict conditions of external investment, trade, and financial sanctions. The paper aims to analyze changes in the technological effectiveness and innovativeness of regional industry, identifying trends that contribute to economic dynamics in conditions of external uncertainty and economic instability. The objectives of the study include the development and testing of a system of indicators for a comprehensive assessment of the effectiveness of industrial and innovative development of regions with different levels of technological structure (the ratio between high/medium/low technology sectors; aggregated – HT, HMT, LMT- and LT-sectors), allowing for comparative studies of regional parameters contributing to the development of the industry in the regime of external restrictions. Research methods include comparative analysis, economic and statistical methods, the use of correlation analysis, etc. The research hypothesis of the study is to substantiate different formats for the development of industrial regions, distinguished by the differentiation of the technological structure of industry, the complementarity of the economic advantages of technological sectors, which allows the region in the conditions of external destabilization to ensure the effectiveness of industrial development and innovative dynamics. As a result of the study, it was revealed that industrial regions have different technological structures and are developing at different rates; the technological competencies of the LMT sector ensure sustainable industrial dynamics in all analyzed regions, and the HT, HMT sectors ensure the preservation of innovative intensity of development. The technological and logical advantages of industries and the combination of technologically heterogeneous sectors are one of the factors that allow the region, under conditions of external restrictions, to simultaneously ensure both effectiveness and promotion of industrial and innovative development. The proposed conclusions and analytics can be used in developing regional industrial policies of the constituent entities of the Russian Federation.