This paper addresses the challenges of rural school bus routing, particularly in scenarios involving heterogeneous fleets and mixed student populations from different schools sharing buses. To tackle these challenges while ensuring both efficiency and safety, a specialized school bus route planning algorithm for heterogeneous fleets and mixed loads (HFML-SBRP) is proposed. First, a mixed-integer programming model is formulated to minimize total operational expenses, including fleet size, fixed costs, and distance-based costs, while adhering to safety constraints. A two-phase solution method is then introduced. The first phase employs a heuristic algorithm that integrates a greedy approach and variable neighborhood search with three neighborhood operators to generate feasible and safe bus routes. In the second phase, an adjusting clock algorithm refines these routes to further reduce the number of buses while maintaining safe and reliable transportation. Experimental results demonstrate that HFML-SBRP effectively minimizes costs, reduces fleet size, and enhances computational efficiency, all while prioritizing student safety.