The current possibilities and trends in the use of the multi-criteria decision-making method in the optimization of a region's logistics infrastructure are analyzed in this chapter. The mathematical model is based on a multi-criteria assessment of the logistic potential of the region. The authors' optimization approach to the design and development of the regional logistics system's infrastructure will not only reveal the possibilities of the regional logistics resources, but will also contribute to the active integration of Russian regions into the system of internal and international transport corridors. This, in turn, will create new opportunities for the implementation of the region's economic development strategy and integration into world economic relations.