Background: Jaw-in-a-Day (JIAD) procedures with fibula free flap (FFF) reconstruction offer immediate aesthetic and functional rehabilitation for maxillofacial defects. However, postoperative trismus and prosthetic complications remain common, particularly in patients undergoing radiation therapy. This study investigated key anatomical and therapeutic predictors of trismus and their implications for prosthetic planning in JIAD cases. Methods: A mixed-methods design was utilized, comprising (1) a systematic review of trismus in head and neck cancer patients, (2) a retrospective CBCT morphometric analysis of mandibular anatomy, and (3) a prospective clinical cohort study comparing trismus severity among control, FFF-only, and FFF with radiation therapy (FFF+RT) groups. The systematic review was registered in PROSPERO (CRD420250651084) and conducted per PRISMA guidelines. Both CBCT and clinical components received IRB approval from the University of Pennsylvania. Results: The review identified radiation dose—particularly >50 Gy to masticatory muscles—as a major risk factor, with trismus incidence peaking around six months post-treatment. IMRT was associated with lower trismus rates than conventional RT, and structured jaw exercises showed preventive benefits. Clinical data confirmed significantly reduced jaw mobility in the FFF+RT group. CBCT analysis revealed consistent mandibular dimensions, supporting prosthesis height estimation and surgical planning. Finger-width assessments correlated strongly with objective measurements. Conclusion: Trismus risk in JIAD patients is driven by radiation exposure, anatomical variation, and reconstructive technique. Integrating morphometric analysis, functional screening, and preventive strategies into treatment planning may improve long-term outcomes. These findings underscore the importance of individualized, interdisciplinary approaches in optimizing complex jaw reconstruction.