Changing geopolitical environment in the world determines the chief priority of existence and development of the state, which is maintenance of the national sovereignty based on economic, technological and financial autonomy and independence. The basis of economic security of the country is the manufacturing sector. The study is devoted to identifying the ability of manufacturing sector of those industrial regions of Russia where manufacturing industry occupies a significant share of economics to maintain stability in conditions of external pressure since 2008 on the example of crises of various nature. The basic methods applied in the study are the indicative and comparative methods and the correlation analysis method. The authors present the analysis of the dynamics of the main indicators of development of the manufacturing sector of industrial regions of Russia, their investment and innovation activity in the industry and territorial perspective and the dependence of the regions’ development on foreign trade. It is pointed out that industrial regions are still of great significance in the development of manufacturing sector of the Russian Federation but their share in Russia is declining in such key indicators as gross regional product, volume of goods shipped, number of employees, etc. The authors conclude that in the majority of industrial regions high investment activity in manufacturing sector has greatly provided for sufficient resilience level which ensured rapid restoration of production volumes after 2008 crisis and smooth adaptation to the growing sanctions pressure that started in 2014. At the same time in nine of the 23 industrial regions under study, manufacturing sector was able to cope with the short-term shock of 2008 but prolonged impact of external factors that started in 2014 resulted in a slowdown in the trajectory of development. However, there is a risk of growing systematic character of the crisis in these regions, and it requires changing the approaches to the existing industrial policy and conducting additional analysis and assessment of the efficiency of the government support measures for manufacturing sector in order to develop the most effective industrial policy for every separate region. The results of the study can be useful for regional and federal authorities implementing economic and industrial policy.