The main purpose of the study is to model the prospects for sustainable development of the region due to smart specialization in the system of ensuring innovative security. The methodology includes a diverse number of techniques that contributed to the achievement of the desired result. In particular, general theoretical methods of analysis, the method of comparing the key characteristics of the studied regions, the method of correlation and regression analysis were used. As a result of the study, the density of the influence of various factors (characteristics of the functioning of the educational and scientific components, indicators of the innovative activity of the business environment of the region) on the dynamics of changes over time in the performance indicators of a particular region was studied. According to the authors, this study can become a guide for regional authorities in developing an implementation plan and relevant roadmaps for the implementation of practical strategies for sustainable development of the region. The study has limitations and they relate to the inability to cover an indicative number of regions. Each region is individual and requires a separate approach. The practical value of the calculations carried out lies in the disclosure of those components and characteristics of the educational, scientific, and industrial activities of the region, the direction of efforts and resources for the activation of which will allow the region to get a guaranteed positive result through the growth of the gross regional product and the available income of the region due to an indicative increase in innovation security.