Digital re-industrialization of depressed regions of the Russian Federation is a strategically significant process aimed at implementing a set of measures to introduce digital technologies in industrial production, the purpose of which is to stimulate economic growth and improve the competitiveness of these territories. This process is particularly relevant in the context of the need to overcome structural imbalances and socio-economic problems in depressed regions, as well as in the context of increasing globalization and technological transformation of the world economy. The purpose of the study is to assess digital re-industrialization in depressed regions of the Russian Federation with a focus not only on the modernization and transformation of existing traditional industrial sectors with the help of digital technologies, but also on the creation of new digital industries. The basis for the analysis was Rosstat data for 2022–2023, as well as the materials of the Strategies of Digital Transformation of the constituent entities of the Russian Federation. As a result of the study, a methodology for assessing digital reindustrialization, adapted to the special conditions of depressed regions of the Russian Federation, was developed and tested, demonstrating how the processes of digital reindustrialization affect the economic development of depressed regions. The novelty of the author’s concept of digital re-industrialization lies in its consideration on the basis of the convergence of digital industrialization and industrial digitalization. In some regions, digital transformation promotes accelerated modernization and growth, while in others it faces a number of obstacles related to limited resources and infrastructural problems. The practical value of the study is expressed in the recommendations for stimulating economic resilience of depressed regions of the Russian Federation. The authors’ further research will be aimed at expanding the empirical database. It also seems important to integrate the presented methodology with other digital strategy tools. It is necessary to conduct long-term monitoring of the results of the implementation of strategies of digital transformation of depressed regions, taking into account the specifics of each region. A promising direction is the study of interregional interaction and the creation of conditions for the dissemination of best practices of digital reindustrialization.