Vehicle routing optimization (VRO) designs the best routes to reduce travel cost, energy consumption, and carbon emission. Due to non-deterministic polynomial-time hard (NP-hard) complexity, many VROs involved in real-world applications require too much computing effort. Shortening computing time for VRO is a great challenge for state-of-the-art spatial optimization algorithms. From a spatial-temporal perspective, this paper presents a spatial-temporal Voronoi diagram-based heuristic approach for large-scale vehicle routing problems with time windows (VRPTW). Considering time constraints, a spatial-temporal Voronoi distance is derived from the spatial-temporal Voronoi diagram to find near neighbors in the space-time searching context. A Voronoi distance decay strategy that integrates a time warp operation is proposed to accelerate local search procedures. A spatial-temporal feature-guided search is developed to improve unpromising micro route structures. Experiments on VRPTW benchmarks and real-world instances are conducted to verify performance. The results demonstrate that the proposed approach is competitive with state-of-the-art heuristics and achieves high-quality solutions for large-scale instances of OPEN ACCESS ISPRS Int. J. Geo-Inf. 2015, 4 2020 VRPTWs in a short time. This novel approach will contribute to spatial decision support community by developing an effective vehicle routing optimization method for large transportation applications in both public and private sectors.