The management of craniofacial discrepancies requires integrated understanding of how orthopedic and orthodontic interventions interact biomechanically to modify skeletal growth and achieve stable dentofacial outcomes. This review synthesizes current knowledge on the biomechanical principles underlying craniofacial growth modification, examining how force systems interact with facial sutures, the temporomandibular joint, and alveolar bone to produce therapeutic change. The aim is to provide clinicians and researchers with a comprehensive framework for understanding the mechanical determinants of treatment response and their translational implications for patient-centered care. The analysis integrates foundational concepts from skeletal and dentoalveolar biomechanics with contemporary advances in skeletal anchorage, digital treatment planning, and hybrid appliance systems. Key biomechanical frameworks examined include force-vector optimization, load distribution patterns, and the differential tissue responses of sutural, condylar, and periodontal structures to mechanical stimuli. Clinical applications are reviewed across major growth modification modalities including functional appliances, orthopedic expansion, temporary anchorage device systems, and surgical-orthodontic coordination. Comparative evaluation of treatment approaches reveals that optimal outcomes depend on appropriate matching of mechanical strategy to skeletal maturity, vector control precision, and anchorage stability. Methodological considerations for treatment assessment emphasize the need for standardized biomechanical outcome measures and long-term stability evaluation. Challenges and future directions include predictive growth modeling, AI-assisted biomechanical simulation, and personalized treatment algorithms. The review concludes that integrated orthopedic-orthodontic management, grounded in sound biomechanical principles and enabled by emerging technologies, offers the most reliable pathway to predictable, stable, and minimally invasive correction of craniofacial discrepancies.