The sanctions imposed on the Russian economy predetermine the risks of reduced control and localization of cross-border gateways servicing international payments. In these conditions, an important element of state economic policy is the development of adaptive solutions that ensure the possibility of minimizing the risks of transformation of foreign economic activity. One of the mechanisms that form the basis for solving this problem is the use of decentralized finance (DeFi) in the practice of international settlements. Meanwhile, it should be noted that in this area of financial and economic relations today there are a number of open questions—from the conceptual apparatus to aspects of studying the impact of these fintech technologies on the prospects for the sustainability of national financial systems and economic development in general. These issues are especially relevant at the regional level. This article is devoted to an attempt to find answers to them. In it, based on the systematization of macroeconomic effects arising within the framework of the potential transition of regional economic systems to the practice of using DeFi in transnational settlements, a macroeconomic model is developed. It is based on a system for searching for externalities that assess the sensitivity coefficients of the financial and economic system of a region to the hypothetical use of DeFi instruments in the system of organizing transnational settlements under the conditions of sanctions restrictions on the use of traditional financial instruments.