Cleidocranial dysplasia, a rare genetic disorder primarily caused by Runt-related transcription factor 2 (RUNX2) heterozygous mutation, serves as a representative model for investigating regulatory mechanisms of RUNX2 in bone remodeling and tooth eruption. As a master transcription factor governing mineralized tissue development, RUNX2 orchestrates bone remodeling and tooth eruption through diverse regulatory networks. It drives alveolar bone formation via transcriptional activation, integration of multiple signaling cascades, and epigenetic modifications, thereby generating the biomechanical force for tooth eruption. Concurrently, RUNX2 promotes osteoblastic secretion of osteoclastogenic factors and directly regulates osteoclast precursor differentiation, facilitating bone resorption at the coronal aspect of dental follicles to estavlish the eruption pathway. Furthermore, RUNX2 modulates eruption progression by participating in stress-induced biological signal transduction within dental follicle cells (DFCs), remodeling the DFCs microenvironment, and regulating DFCs senescence. RUNX2 also influences root development via the NOTUM-Wnt axis, providing auxiliary biomechanical conditions conducive to eruption. This review systematically delineates the pivotal role of RUNX2 in coordinating bone remodeling and tooth eruption. Future studies should leverage organoid models and multi-omics technologies to further elucidate the spatiotemporal regulatory networks of RUNX2, potentially advancing precision diagnostics and therapeutics for rare skeletal-dental developmental disorders.