The relevant pressure exerted on ports following the advent of globalization and containerization has contributed to transform the role of such intermodal transport facilities, increasing their complexity with reference to both performed activities and involved actors. The potential of solid hinterland connections in enhancing port competitiveness has sustained the larger embracement of the railway mode, which has proved to be a financially and environmentally sustainable solution, especially on long hauls. However, the limited residual capacity currently characterizing several railway network and nodes may threaten the accommodation of additional future traffic volumes and, thus, it requires the adoption of a coordinated strategy to more efficiently manage existing railway infrastructures, other than the realization of some new ones. In this regard, an integrated methodology has been developed to specifically model, simulate and optimize port railway processes, as part of a more complex system, imposing the maximization of capacity with the concurrent minimization of used shunting locomotives, to varying of infrastructural and operational conditions. This combination of techniques has been applied to the case study of the Port of Trieste, Italy, showing the greater influence of tracks availability over changes in the operational conditions, in terms of a shorter duration of specific administrative tasks and the employment of more shunting locomotives.