In general, import and export flows are not processed at equal rates in hub facilities. In addition, the hub is a complex facility operating with several types of limited resources and in which import and export vehicles might not be synchronized. These aspects are usually not properly incorporated into existing hub network design models. To address these issues, we introduce the idea of generalized capacity constraints and propose two mixed-integer linear programming models to incorporate these constraints, together with a heuristic. We also provide a methodology for estimating capacity-related parameters in the context of intermodal rail-road hub network design considering non-synchronized train–truck operations. The formulations are evaluated on the well-known AP data set, and we discuss the case study of a projected intermodal transportation system in Colombia in which the transshipment equipment and storage space availability are considered limiting hub resources. Our analysis suggests the most efficient formulation for the problem and the efficiency and effectiveness of the proposed heuristic. It is also observed that synchronization has an important impact on the total costs affecting the hub network structure.