Distraction osteogenesis (DO) is commonly used for bone regeneration, but its application in irradiated bone remains challenging due to compromised healing capacity. A 28-year-old male with a severe mandibular defect after tumor extensive resection and radiotherapy was reported in this study. Computer-assisted surgical planning was used, along with modified protocols: a slower distraction rate and extended consolidation. A pathological fracture occurred during distraction but was successfully managed with adjunctive hyperbaric oxygen therapy, ultimately achieving sufficient bone formation for dental implant placement. This experience combined with current evidence from the literature highlights clinical challenges and strategies for DO in irradiated bone, offering references for clinicians managing similar complex cases.