Order distribution and routing optimization of takeout delivery is a challenging research topic in the field of e-commerce. In this paper, we propose a drone–rider joint delivery mode with multi-distribution center collaboration for the problems of limited-service range, unreasonable distribution, high delivery cost, and tight time windows in the takeout delivery process. The model is constructed with the minimum delivery cost and the overall maximum customer satisfaction as the objective function, and a two-stage heuristic algorithm is designed to solve the model. In the first stage, Euclidean distance is used to classify customers into the regions belonging to different distribution centers, and the affinity propagation (AP) clustering algorithm is applied to allocate orders from different distribution centers. The second stage uses an improved tabu search algorithm for route optimization based on specifying the number of rider and drone calls. This paper takes China’s Ele.me and Meituan takeout as the reference object and uses the Solomon data set for research. The experimental results show that compared with the traditional rider delivery mode, the drone–rider joint delivery mode with multiple distribution center collaboration can effectively reduce the number of riders used, lower the delivery cost, and improve the overall customer satisfaction.