Given the swift expansion of fresh e-commerce, the front warehouse mode can respond quickly and ensure the quality of fresh products. However, the complexity of the supply chain structure under front warehouse mode poses a challenge in reducing logistics costs and improving distribution efficiency while meeting consumers’ immediate delivery demands. Therefore, this paper studies the vehicle routing problem of two-echelon fresh e-commerce under front warehouse mode. Considering trans-shipment time constraints between the two echelons and the characteristics of terminal distribution, this paper initially models the vehicle routing problem for front warehouses as a two-echelon multi-trip capacitated vehicle routing problem with time windows. A mixed-integer linear programming model is subsequently established. To solve the model, a hybrid genetic algorithm integrated with neighborhood search is developed. Matrix coding is employed to merge vehicle selection and route assignment decisions. Simultaneously, neighborhood search is applied to enhance the search capability of algorithms, thereby improving the quality of solutions. Furthermore, the effectiveness and efficiency of the model and algorithm are verified through experiments of varying scales. Finally, comparative strategies and sensitivity analysis highlight the advantages of multi-trip strategies and provide insights into the optimal vehicle capacity limit.