A large amount of cargo is transported between European and Southeast Asian countries. Ships sometimes take different routes when sailing between ports due to the best commercial speed; navigational, economical, and hydrometeorological conditions; and political and military situations. Several routes are available for sailing between Europe and Southeast Asia: sailing the Suez Canal, sailing around the African continent, sailing the Panama Canal, as well as sailing the Northern Sea route. This article analyzes the possible sailing routes between Southeast Asia and Europe and presents a developed methodology for the evaluation of sailing routes. This sea route evaluation methodology is based on a comparative mathematical model that evaluates the main factors of cargo transportation by sea: transportation cost and time, possible maximum ship parameters, transportation energy (fuel) demand, and other possible factors, such as the probability of various restrictions. This paper presents a case study of cargo transportation between Rotterdam (The Netherlands) and Shanghai (China) using different possible sea routes. Assessments of various possible routes are presented; the main topics of discussion and conclusions are formulated.