Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, necessitating the continuous evolution of effective cardio protective pharmacotherapy. The complexity of cardiovascular pathophysiology, involving endothelial dysfunction, oxidative stress, inflammation, lipid dysregulation, and thrombosis, demands a multifaceted therapeutic approach. Conventional pharmacological agents such as antihypertensive, statins, antiplatelet drugs, and anticoagulants have significantly improved clinical outcomes by targeting key mechanisms involved in disease progression. In recent years, emerging drug classes including sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and angiotensin receptor-neprilysin inhibitors (ARNIs) have demonstrated additional cardio protective benefits beyond their primary indications.The integration of nanotechnologybased drug delivery systems has further enhanced drug bioavailability, targeted delivery, and therapeutic efficacy while minimizing adverse effects. Clinical perspectives emphasize evidence-based approaches, personalized medicine, and pharmacogenomics to optimize treatment outcomes and reduce variability in drug response. Despite significant progress, challenges such as drug resistance, adverse effects, and patient non-adherence persist. This review provides a comprehensive overview of the mechanistic basis and clinical relevance of cardio protective pharmacotherapy, highlighting recent advances and future directions aimed at improving cardiovascular health outcomes globally