Ameloblastomas are slowly growing, locally invasive tumors with high recurrence rate and more common in the mandible, if not treated they can grow to enormous size. Radical resection is the only predictable form of treatment for ameloblastomas. However, mandibular resection can lead to dysfunctions in appearance, speech, mastication, and deglutition, which severely impair the patients’ quality of life. The reconstruction of extensive bone defects in the maxillofacial area is still challenging. To meet the demands of functional reconstruction, minimizing the negative influence of mandibular malformation, and disability on patients, the individualized systematic treatment plans highlight denture prosthodontics and require much consideration of multidisciplinary cooperation, with such related fields as maxillofacial surgery, oral implantology, prosthodontics, and radiology taken into account. In this report, we will present a case of reconstructing the mandibular segmental defect after the resection of a rarely giant ameloblastoma. In the case, we took the restoration of the missing teeth and the rehabilitation of the masticatory function as well as restoring bony continuities and facial appearance into consideration, communicated well with prosthodontists and implantologists before surgery, making the individualized systematic treatment plan more effective and efficient.