As the market of express delivery services expands rapidly, delivery service companies are exposed to severe competition. As a result of the surplus of delivery companies, they are struggling with remaining competitive at a reasonable price with appropriate level of customer satisfaction. To cope with competition pressures, a strategic alliance is suggested as an effective solution to the challenges faced by small and medium enterprises (SMEs) in express delivery services. Therefore, this study suggests a combined optimization and simulation approach to the reconfiguration of an express delivery service network for strategic alliance with respect to strategy partnership of closing/keeping service centers among companies involved and adjustments of their cutoff times. An illustrative numerical example is presented to demonstrate the practicality and efficiency of the approach.