Researchers and practitioners argue that in the global context of the Fourth Industrial Revolution, also labelled Industry 4.0, the regional dimension of industrial development remains equally essential. A region that effectively implements the concept of Industry 4.0 can accelerate by enhancing the manufacturing energy efficiency, thus contributing to the goals of the “Green Deal” policy. Therefore, to support the policy-making process, it is necessary to develop analytical tools exploring the determinants of the Industry 4.0 development. This paper presents a methodology of strategic analysis of a region in terms of the Industry 4.0 development potential. The core of the methodology is an extended Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. The study identifies regional strengths and weaknesses, external incentives and disincentives, internal opportunities and threats, and external opportunities and threats with regard to the development of Industry 4.0, related technologies and the potential of increasing manufacturing energy efficiency. The research procedure is exemplified by the case of Podlaskie Voivodeship in Poland. The results of this study demonstrate the robustness of the proposed approach. The elaborated methodology can be used by decision-makers in designing strategies for the development of fourth-generation industry at a regional level.