In the take-out food industry, improper path planning by couriers often leads to low delivery efficiency. Most of the existing VRP research focuses on the optimization of express delivery and other industries, and there is a lack of optimization algorithm research for the food delivery with real-time characteristics. Aiming at the Online to Offline (O2O) take-out delivery routing optimization problem, this paper takes a comprehensive consideration of its dynamic delivery requirements, cargo differentiation and other characteristics as well as constraints such as time windows and cargo capacities, and establishes an O2O dynamic route optimization model of the take-out delivery personnel, in which the business districts are regarded as a delivery centre, and the number of delivery personnel and the total travel time by the delivery personnel are taken as the minimization targets. Using the method of periodically processing new orders, the resultant dynamic adjustment problem of the delivery personnel's route is converted into a series of static TSP sub-problems and thereby a phased heuristic real-time delivery routing optimization algorithm framework is designed, and a concrete algorithm and a numerical example are given. A set of test cases centered on business districts is generated on the basis of a number of widely used VRP instances, the algorithm is tested through simulation experiment and compared with other algorithms. The results show that the algorithm proposed in this paper can make full use of the delivery personnel near the location of the new orders to conduct the delivery, optimize the corresponding delivery route, and effectively reduce the number of delivery personnel for delivery and the total travel time by the delivery personnel.