Bone disorders affect more than half of the adult population worldwide who may have a poor quality of life and physical independence worldwide. Multi-omic techniques are increasingly adopted and applied to determine the molecular mechanisms of bone tissue repair, providing perspective towards personalized medical intervention. Data from genomics, epigenomics, transcriptomics, proteomics, glycomics, and lipidomics were combined to elucidate dynamic processes in bone repair. In this narrative review, the key role of genetic and epigenetic factors in regulating injured cellular responses is highlighted, and changes in RNA and protein expression during the healing phase, as well as glucolipid metabolism adaptation, are described in detail how the repair process is affected. In a word, the integration of multi-omic techniques in this review not only benefits the comprehensive identification of new biomarkers, but also facilitates the development of personalized treatment strategies of bone disorders to revolutionize regenerative medicine.