Stem cell therapy in heart disease is challenged by mis-injection, poor survival, and low cell retention. Here, we describe a biocompatible multifunctional silica-iron oxide nanoparticle to help solve these issues. The nanoparticles were made via an in situ growth of Fe₃O₄ nanoparticles on both the external surfaces and pore walls of mesocellular foam silica nanoparticles. In contrast to previous work, this approach builds a magnetic moiety inside the pores of a porous silica structure. These materials serve three roles: drug delivery, magnetic manipulation, and imaging. The addition of Fe₃O₄ to the silica nanoparticles increased their colloidal stability, T₂-based magnetic resonance imaging contrast, and superparamagnetism. We then used the hybrid materials as a sustained release vehicle of insulin-like growth factor-a pro-survival agent that can increase cell viability. In vivo rodent studies show that labeling stem cells with this nanoparticle increased the efficacy of stem cell therapy in a ligation/reperfusion model. The nanoparticle-labeled cells increase the mean left ventricular ejection fraction by 11 and 21% and the global longitudinal strain by 24 and 34% on days 30 and 60, respectively. In summary, this multifunctional nanomedicine improves stem cell survival via the sustained release of pro-survival agents.