The sanctions imposed on the Russian Federation (hereinafter referred to as RF, Russia) have most significantly affected high-tech sectors of the economy. In these conditions, it is necessary to solve a number of problems, including import substitution, the transition to the Industry 4.0 concept and low-carbon production and consumption. The need of participation in solving these problems is substantiated not only for large, but also for small and medium-sized businesses (hereinafter referred to as SMB). The current state and prospects for the development of small and medium-sized enterprises (hereinafter referred to as SME) in Russia are analysed. The article emphasises the discrepancy between the modern state of the domestic SME and its potential capabilities , in particular the insufficient participation of this business in production activities. The problems of SMB and its risks related to the current geopolitical situation are indicated. Ways of overcoming similar problems in other countries experiencing sanctions pressure, as well as the efforts of the RF to minimise losses of the Russian SMB, are shown. It is noted that the implementation of the national project “Small and medium-sized entrepreneurship and support for individual entrepreneurial initiative” does not solve all the problems of the SME. As promising areas for the SMB development, it is proposed to strengthen its cooperation with big business, modify the “Grow a Supplier” programme, and intensify work on targeted training of personnel for subjects of small and medium-sized manufacturing entrepreneurship in the country’s universities with participation of the big business. The ways to ensure the sustainability of the domestic manufacturing business, possible in modern conditions, are considered.