To explore the optimization problem of container multimodal transportation routing, considering the uncertainty in the process of transportation and transshipment. Firstly, the uncertainty of service time corresponding to different and same departure times in the multimodal transportation process was analyzed. Secondly, a multimodal transportation routing optimization model was established, with the constraints of the time windows for transfer nodes and the delivery deadline, the departure time being a decision variable, and aiming to minimize the sum of transportation costs, transshipment costs, storage costs, in-transit inventory costs, delay costs, and carbon emission-related costs. Finally, a multimodal transportation simulation model was established, and the optimization model was jointly solved to obtain the optimal transportation routing plan considering uncertainty using AnyLogic simulation software and OptQuest optimization solver. Taking the Xiaoqing River Navigation Restoration Project in Shandong Province as an example, a container transportation route between Shandong Province and South Korea and Japan was established. By comparing optimal multimodal transportation routing plans and departure times considering determined and uncertain time, it is found that the optimization plan under uncertainty is a more stable and reliable routing plan. This also demonstrates the feasibility of solving the multimodal transportation routing optimization problem under uncertainty using simulation-based optimization.