The vehicle routing problem with simultaneous deliveries and pickups (VRPSDP) has attracted much research interest because of the potential to provide cost savings to transportation and logistics operators. Several extensions of VRPSDP exist. Of these extensions, the simultaneous deliveries and pickups with split loads problem (SDPSLP) has been proposed to eliminate vehicle capacity constraints, as well as allow the deliveries or pickups for a customer to be split into multiple visits. Although delivery and pickup activities are often constrained by time windows, few studies have considered such constraints when SDPSLP has been addressed. To fill the gap, this paper formulates the vehicle routing problem of simultaneous deliveries and pickups with split loads and time windows (VRPSDPSLTW) as a mixed-integer programming problem. A hybrid heuristic algorithm was developed to solve this problem. Solomon data sets with minor modifications were applied to test the effectiveness of the solution algorithm. The results of a computational experiment demonstrated that use of the proposed algorithms to solve VRPSDPSLTW had advantages for minimization of the total travel cost, number of vehicles, and loading rate. The proposed formulation and solution algorithm for VRPSDPSLTW may serve as a general analytical tool for the optimization of vehicle routing in practice.