The wide arena of applications opened by nanotechnology is multidimensional. It is already been proven that its prominence can continuously influence human life. The role of stem cells in curing degenerative diseases is another major area of research. Cardiovascular diseases are one of the major causes of death globally. Nanotechnology-assisted stem cell therapy could be used to tackle the challenges faced in the management of cardiovascular diseases. In spite of the positive indications and proven potential of stem cells to differentiate into cardiomyocytes for cardiac repair and regeneration during myocardial infarction, this therapeutic approach still remains in its infancy due to several factors such as non-specificity of injected cells, insignificant survival rate, and low cell retention. Attempts to improve stem cell therapy using nanoparticles have shown some interest among researchers. This review focuses on the major hurdles associated with cardiac stem cell therapy and the role of nanoparticles to overcome the major challenges in this field, including cell modulation, imaging, tracking and gene delivery.