The unsatisfactory dynamics and high level of volatility of economic processes actualize the problem of ensuring the stable development of regional systems. The economic situation in the Federation largely depends on the state of the manufacturing industry, which is the main branch of Russian regions specialization. The aim of the work is to study the sustainability of the regional economy in the face of shocks in 2014–2015. The research methodology includes an analysis of domestic and foreign literature on the sustainability of the regional economy. A comprehensive analysis of scientific literature has shown that in an unstable economy, the importance of studying the issues of economic resilience, i.e. its ability to withstand external shocks, as well as quickly recover in the post-shock period, increases. To identify the impact of external shocks on the dynamics of manufacturing industries, two periods are identified: 2012–2014 and 2016–2018. The analysis was carried out using official data from the Federal State Statistics Service of the Russian Federation. The paper studies the resistance of manufacturing industries in the regions of the Central Federal District and the Northwestern Federal District to the impact of shocks. Based on the level of resilience, the regions are divided into three groups. In the regions of the first group, the industrial production index reached the pre-crisis level; in the second group, it exceeded the pre-crisis level, and in the third one, the dynamics of manufacturing industries worsened. The analysis did not reveal any significant influence of the factors of specialization and innovative activity on the level of shock resistance. Regions with the same specialization showed significantly different levels of shock resistance. In the context of a low level of innovation and investment activity, it is difficult to draw a conclusion about any significant impact of innovation on the adaptation of regions to the post-shock economy conditions. At the same time, as the analysis has shown, most regions with higher growth rates of manufacturing industries in the post-crisis period have a positive dynamics of innovation activity. Manufacturing industries in most regions have adapted to the new economic reality. At the same time, the low level of investment and innovation activity does not allow us to conclude that adaptation was accompanied by an increase in the technological level of the industry.