Given the high costs of construction and maintenance, an optimum design methodology is one of the most important steps towards the development of transportation infrastructure, especially freeways. However, the effects of different variables on the decision-making process to find an optimal variant have caused the choice to become a very difficult and professional task for decision makers. So, the current paper aims to determine the optimal variant route for Isfahan-Shiraz freeway through MADM approaches. First, evaluation indices for an optimal route variant are derived through literature review and expert panel assessment. Then, a dynamic fuzzy GRA method is used for weightings and optimal route selection. Bases on the results, the road longevity, views of NGOs and route integration are identified as the highest-weighted criteria in route variant prioritization. Further, Route 3 is defined as the priority for the optimal variant for Isfahan–Shiraz freeway, which is the main basis in practice.