<p>Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with myocardial infarction (MI) and subsequent heart failure (HF) posing significant clinical challenges. Despite advancements in pharmacological and surgical interventions, the limited regenerative capacity of the adult human heart necessitates innovative therapeutic strategies. Stem cell-based therapies have emerged as a promising approach to cardiac regeneration, aiming to restore damaged myocardial tissue through cell replacement and paracrine-mediated repair mechanisms. This review provides a comprehensive overview of the current landscape of stem cell therapies for cardiac regeneration, focusing on the molecular mechanisms, cell types, delivery techniques, and recent clinical advancements. We highlight the roles of key signaling pathways, including NOTCH, PI3K/Akt, Wnt/β-catenin, Hippo/YAP, and MAPK, in regulating cardiomyocyte proliferation, angiogenesis, fibrosis, and inflammation. Additionally, we discuss the therapeutic potential of various stem cell types, such as mesenchymal stem cells (MSCs), cardiac progenitor cells (CPCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs), in promoting cardiac repair. Despite promising preclinical results, challenges such as low cell retention, immune rejection, and inconsistent clinical outcomes persist. Recent advancements in genetic engineering, and innovative delivery methods, including transendocardial and intracoronary injections, offer new avenues for enhancing therapeutic efficacy. This review underscores the need for further research to optimize stem cell-based therapies, improve clinical trial design, and translate these innovative approaches into effective treatments for heart disease. By addressing these challenges, stem cell therapy holds the potential to revolutionize cardiac regeneration and improve outcomes for patients with ischemic heart disease and heart failure<b>.</b></p>