Extracellular adenine nucleotides serve as crucial signaling molecules and influence a broad spectrum of physiological and pathological processes. CD73, the rate-limiting enzyme in the metabolism of extracellular adenine nucleotides, is ubiquitously expressed on various cell types, particularly stem cells. CD73 mesenchymal stem cells (MSCs) have emerged as promising candidates for therapeutic applications due to their immunomodulatory and pro-regenerative properties. Numerous studies have highlighted the crucial role of CD73 in mediating tissue protection in myocardial infarction (MI). In this review, a brief overview of the cell type-specific expression, regulatory effects of CD73 on MSCs, and proangiogenic and immunomodulatory mechanisms is provided, with a focus on current findings concerning the protective functions of CD73 in the context of MI within the framework of stem cell therapy.