Despite the growing importance of science, technology and innovation (STI) in socio-economic progress, various external challenges are increasingly affecting STI in many countries. Russia, just starting to emerge from the socio-economic recession caused by the COVID-19 pandemic, at the beginning of 2022 faced even stronger external threats related to the introduction of powerful political and economic sanctions against it. This required a significant adjustment of state policy in relation to various sectors of the economy, including STI. This chapter discusses the trends in Russia’s STI development, as well as the processes of transformation of the national STI policy agenda aimed at overcoming new challenges.