Medication distribution service can be delivered based on a combination of home delivery and customer pickup. That is, medications are delivered either to customers’ homes directly or to the pickup facilities (e.g. lockers) close to customers’ homes. In Taiwan, there are more than 11,000 convenience stores that provide a 24-h service for customers to pick up the ordered items from e-commerce, which is unique to the world. In the medication distribution system, convenience stores can provide a unique opportunity for customers to more conveniently collect medications at stores, and also can reduce the operating cost for a logistics company providing the medication delivery service. Therefore, this work proposes a medication distribution system through convenience stores, lockers, and home delivery. Under this system, this work investigates how to simultaneously determine employment of convenience store chains, the convenience store locations to be visited, locations of lockers, vehicle routes for convenience stores and lockers, and vehicle routes for customers’ homes, so that the total operating cost is minimized. This work further proposes a genetic algorithm to solve the medication distribution problem. Through simulation, the experimental results show that the proposed algorithm is able to solve the problem efficiently.