Mesenchymal stem cells are used most in regenerative medicine due to their capacities in differentiation and immune modulation. The intraosseous injection of MSC into the bone has been recommended because of expected outcomes for retention, bioavailability, and enhanced therapeutic efficacy, particularly in conditions involving the bone, such as osteoporosis and osteonecrosis. A review of the intraosseous delivery of mesenchymal stem cells in comparison with intravenous and intra-arterial delivery methods will be subjected to critical examination. This delivery mode fares better regarding paracrine signaling and immunomodulation attributes, which are the cornerstone of tissue regeneration and inflammation reduction. The local complications and technical challenges still apply with this method. This study was more focused on further research soon to be conducted to further elucidate long-term safety and efficacy of intraosseous mesenchymal stem cell therapy. Though much has been achieved with very impressive progress in this field, it is worth noting that more studies need to be put into place so that this technique can be established as a routine approach, especially with further research in biomaterials, gene therapy, and personalized medicine.