The current stage of development of the Russian economy is characterized by the priority of achieving technological sovereignty. An important role in addressing this challenge is assigned to the regional level, which brings to the fore a set of issues related to improving the effectiveness of scientific, technological, and innovation (STI) policy at the regional level. The aim of the study is to assess and substantiate directions for improving the effectiveness of regional STI policy. An analysis of scientific literature reveals that the attributes of this policy include its goals, main implementation areas, principles, and indicators. To evaluate STI policy, the study employs indicators such as “share of research and development expenditures in GRP” and “proportion of organizations engaged in technological innovations”. To investigate the correlation between the indicators, a clustering of the constituent entities of the Russian Federation was performed, resulting in the identification of six groups of regions that differ in R&D expenditures and innovation activity levels. Only 13 regions, forming the first and second clusters, demonstrate relatively balanced development of the scientific and technological sector. However, even in these regions, the level of organizational innovation activity remains low. The largest cluster (30 regions) includes regions that are lagging in STI policy, exhibiting low levels of both technological innovation and R&D expenditures. The development of manufacturing industries is substantiated as the main direction for improving the effectiveness of regional STI policy. Using the shift-share analysis method, an assessment of regional factors of their competitiveness was carried out. Based on these factors, the regions have been divided into five groups. Positive development factors for manufacturing industries were found in regions of the first and second groups (19 regions in total). Nevertheless, most of these regions are not among the industrially developed ones. The largest group (40 regions), which includes leading manufacturing centers, exhibits neutral competitiveness factors. To assess the relationship between regional competitiveness factors and their STI development indicators, a typology of regions was created based on indicators of regional competitiveness factors, R&D, and innovation. It is worth noting that regions with relatively high performance in science and innovation exhibit neutral and negative local factors affecting the development of manufacturing industries. This situation highlights the existence of systemic issues in the development of manufacturing industries in the Russian Federation.