Large defects in the maxillae and mandible, whether congenital or acquired through major surgery, completely alter the dynamics of the stomatognathic system, resulting in a patient who requires complete oral rehabilitation. This case report presents the successful rehabilitation of a 45-year-old male patient who underwent a hemimandiblectomy for extensive osteomyelitis involving the left ramus, condyle, coronoid, and a part of the body of the mandible extending from the ipsilateral premolar region posteriorly. The design of the maxillofacial prosthesis was carried out with careful attention to prosthodontic principles, including the creation of a lip seal, elimination of mandibular deviation in function, and establishment of facial symmetry.