<p>In response to the rapid growth of e-commerce, fulfillment centers face the challenge of managing an increasing volume of online orders. Unlike traditional logistics, e-commerce involves frequent and smaller orders that require packaging in individual parcel boxes. To simplify the packaging process, e-commerce companies have standardized the sizes of parcel boxes, necessitating the addition of void fills to protect small or fragile items. However, the irregular placement of differently sized items within parcel boxes requires considerable manual effort for void fill insertion. Consequently, automated operations for void fill insertion at the stage of the packaging process in e-commerce fulfillment centers are required. Thus, we propose a comprehensive process for void fill insertion into the parcel boxes, from pre-processing 3D images of the items to planning the route of the void fill insertion robot. To determine the robot’s route, we propose a mathematical optimization model. Due to the model’s inherent complexity, we also develop an efficient heuristic algorithm that offers computational time efficiency. The results of numerical experiments demonstrate that our proposed methodology enhances the efficiency of void fill insertion by resolving issues within a short computation time. Additionally, we provide valuable managerial insights which can help improve the operations in the e-commerce fulfillment centers.</p>