Mesenchymal stem cells (MSCs), including stem cells from the apical papilla (SCAP), hold promise in regenerative medicine due to their immunomodulatory properties and ability to recruit progenitor cells. However, their limited in vivo survival post-transplantation hampers therapeutic efficacy. This work explores strategies to enhance MSC viability through the development of hybrid spheroids and hybrid beads. Hybrid spheroids were formed by associating SCAP with nanoparticles containing rapamycin and NecroX-5, using a magnetic field. These constructs demonstrated improved survival and immunomodulatory activity in vitro and in vivo. To further enhance protection, hybrid beads were developed by encapsulating MSC as spheroids in alginate using microfluidics, enabling in situ formation of small spheroids within biocompatible hydrogel droplets. Incorporation of NecroX-5 NPs supported cell survival. These findings demonstrate the potential of combining nanomedicine, spheroid engineering, and hydrogel encapsulation to improve MSC-based therapies. In conclusion, these two strategies offer a promising avenue for enhancing MSC delivery and survival, advancing the field of cell therapy.