The integration of orofacial myofunctional therapy (OMT) with oral appliances, particularly mandibular advancement devices (MADs), presents a promising multidisciplinary strategy for the treatment of obstructive sleep apnea (OSA) and orofacial dysfunctions across the lifespan. This chapter explores the synergistic potential of combining functional therapy with mechanical interventions to optimize airway patency, enhance orofacial muscle function, and promote craniofacial development. In adults, the combination of OMT and MADs has shown benefits in reducing apnea-hypopnea index (AHI), improving muscular tone, mitigating residual obstructive events, and enhancing treatment adherence and patient-reported outcomes. In pediatric populations, OMT supported by intraoral devices plays a critical role in facilitating proper tongue posture, nasal breathing, and harmonious craniofacial growth. Despite encouraging clinical outcomes, the chapter also addresses key limitations, including the variability in patient adherence, lack of standardized protocols, and the need for individualized assessment, especially in relation to MAD design and therapy goals. The importance of interdisciplinary collaboration and ongoing patient monitoring is emphasized as essential for maximizing therapeutic efficacy and minimizing adverse effects. This integrative approach underscores the need for further research and innovation to support the development of standardized, evidence-based protocols for the combined use of OMT and oral appliances in both adult and pediatric care.