In this article, we introduce the Vehicle Routing Problem with Cross-Docking and Scheduling at the Docking Station (VRPCDSD), which integrates pickup and delivery routing decisions with the cross-docking scheduling of the unloading and reloading of requests. We present a compact Mixed Integer Programming (MIP) formulation and a General Variable Neighborhood Search (GVNS) metaheuristic for the problem. The proposed GVNS employs several routing and scheduling neighborhoods that require problem-specific adjustments due to the integrated characteristic of the problem. Computational experiments indicate that the MIP formulation can solve instances with up to 31 nodes (15 requests) within the specified time limit when using a standard commercial solver. Furthermore, the GVNS metaheuristic can obtain high-quality solutions that at least match those encountered by the solver for the tested instances, achieving considerably large improvements over the latter especially as the number of requests increases. In fact, GVNS is able to find the optimal solution for all the instances for which the optimal is known. In addition, GVNS is a viable alternative for tackling larger instances of VRPCDSD and is very robust in that it obtains low deviations from the best-encountered solutions when multiple executions are performed. We also present some insights on how the different cross-docking operation costs impact the optimal solutions.