The advantage of multimodal transport is that it can deliver the goods to their destination in a reasonable combination of transport modes while ensuring security and punctuality. Multimodal transportation can effectively reduce logistics costs, improve logistics efficiency, and reduce environmental pollution. In the process of multimodal transportation, due to the interference of natural factors (weather, terrain, etc.) and some special human factors, it may have different degrees of impact on the transportation time and transportation safety of different transportation modes. Therefore, when choosing a transportation method, it is necessary to consider the transportation time and transportation safety under the interference. However, the current research on multimodal transport has not considered the impact of external interference on transportation time and transportation safety. Compared with other modes of transportation, external interference has a relatively small impact on railway transportation. Railways can safely deliver goods to their destinations on time. Under the background of China’s huge railway network and advanced heavy-duty technology, this paper establishes a multimodal transport route selection model for considering railway as the core, introduces time penalty cost and damage compensation cost, and takes the lowest comprehensive transportation cost as the model objective under the premise of considering transportation reliability and transportation safety. Finally, taking a multimodal transport network in China as an example, an improved ant colony algorithm is used to solve the model and the results verify the rationality of the model.