This paper develops a multiple period heterogeneous optimization model for intercity bus systems. Spatial and temporal variations of intercity trip demand levels are considered. A heuristic algorithm is developed to seek for the near-optimal hybrid operational strategy, which is composed of a variety of bus route types. To demonstrate the applicability and effectiveness of the proposed model, an imitative case study is performed. It is found that total social cost can be minimized by a spatially and temporally dependent hybrid strategy, which has the advantages of cost savings in comparison with the optimal operational strategy in homogeneous environments. For instance, a good hybrid strategy may serve a specific intercity O-D pair by line hual plus feeder routes during weekdays, whereas by direct routes during weekends.