The personalized regenerative therapeutic strategies applicable in the structural and functional repair of maxillofacial/dental defects are expected to extend beyond the limits of what is currently possible in the management of dentofacial anomalies and treating malocclusions. The application of undifferentiated stem cells (SCs), including signaling molecule control and individualized tissue engineering based on targeted therapies, has been proposed to overcome therapeutic limitations and complications associated with treatments for craniofacial defects, including severe orthodontic discrepancies. This scoping, prospective review discusses comprehensively the current knowledge and prospects for improving clinical outcomes by the application of novel cell-required and cell-free regenerative strategies in biomedicine. The existing evidence, although scant, suggests that patients receiving an orthodontic treatment could benefit from precise tissue augmentation, allowing enhancement of tooth movement generated by orthognathic forces; faster, more predictable alignment of dental arches; optimal management of periodontal complications; and prevention of external root resorption. Ultimately, enriching orofacial tissues and “customizing” the repair of congenital/acquired defects in the craniofacial region can be vastly enhanced to provide a positive therapeutic outcome and improve patients’ quality of life.