The paper discusses the main approaches to determining the optimal route of cargo transportation, including the influence of transshipment points and the features of refrigerated transport. A comprehensive review of methods and approaches that can be used to improve efficiency in the transportation of perishable goods is presented. In the light of ecological aspects of logistics, it is proposed to use “clean” modes of transport at certain stages of the route, for example, the use of electric freight transport for urban delivery and railroads for long-distance transportation. It is also proposed to operate alternative energy vehicles using liquefied natural gas or hybrid trucks and electric trucks. It is noted that the inclusion of environmental parameters in the mathematical model may require the introduction of additional target emission-related functions or additional penalties when passing through areas with environmental restrictions (e.g., “green zones” in large cities).