Macrophage-based therapeutic approaches for cardiovascular diseases have gained significant attention due to their critical roles in inflammation, fibrosis, tissue repair, and regeneration. Macrophages, as key immune cells in cardiac tissue, are involved in maintaining homeostasis, cardiac development, and wound healing. Their polarization into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes influences the progression of cardiovascular diseases (CVDs), including heart failure (HF), atherosclerosis, and myocardial infarction (MI). Understanding macrophage behavior and function is essential for developing targeted therapies that modulate inflammation, fibrosis, and tissue repair in CVDs. In the context of CVDs, macrophages play a pivotal role in the inflammatory response, contributing to the progression of atherosclerosis and the development of fibrotic lesions. In atherosclerosis, macrophages are categorized into inflammatory macrophages, resident-like macrophages, and foamy Trem2+ macrophages, each with distinct functions in plaque formation and stability. In MI, macrophages transition from a pro-inflammatory to a reparative phenotype, facilitating tissue repair and scar formation. However, imbalances in macrophage polarization can lead to adverse outcomes, such as fibrosis and diastolic dysfunction in HFpEF. Macrophage-targeted therapies aim to modulate their function, either by promoting anti-inflammatory polarization or inhibiting pro-inflammatory responses. Strategies include macrophage depletion, autophagy induction, and modulation of chemokine pathways. These approaches have shown promise in preclinical studies, with potential for clinical translation. However, challenges remain in ensuring the safety and efficacy of these therapies, particularly in balancing the dual roles of macrophages in both tissue repair and pathological processes. Ongoing research is focused on developing precise and effective macrophage-based therapies for CVDs, with the goal of improving patient outcomes and reducing the global burden of cardiovascular diseases.Macrophage-based therapeutic approaches for cardiovascular diseases have gained significant attention due to their critical roles in inflammation, fibrosis, tissue repair, and regeneration. Macrophages, as key immune cells in cardiac tissue, are involved in maintaining homeostasis, cardiac development, and wound healing. Their polarization into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes influences the progression of cardiovascular diseases (CVDs), including heart failure (HF), atherosclerosis, and myocardial infarction (MI). Understanding macrophage behavior and function is essential for developing targeted therapies that modulate inflammation, fibrosis, and tissue repair in CVDs. In the context of CVDs, macrophages play a pivotal role in the inflammatory response, contributing to the progression of atherosclerosis and the development of fibrotic lesions. In atherosclerosis, macrophages are categorized into inflammatory macrophages, resident-like macrophages, and foamy Trem2+ macrophages, each with distinct functions in plaque formation and stability. In MI, macrophages transition from a pro-inflammatory to a reparative phenotype, facilitating tissue repair and scar formation. However, imbalances in macrophage polarization can lead to adverse outcomes, such as fibrosis and diastolic dysfunction in HFpEF. Macrophage-targeted therapies aim to modulate their function, either by promoting anti-inflammatory polarization or inhibiting pro-inflammatory responses. Strategies include macrophage depletion, autophagy induction, and modulation of chemokine pathways. These approaches have shown promise in preclinical studies, with potential for clinical translation. However, challenges remain in ensuring the safety and efficacy of these therapies, particularly in balancing the dual roles of macrophages in both tissue repair and pathological processes. Ongoing research is focused on developing precise and effective macrophage-based therapies for CVDs, with the goal of improving patient outcomes and reducing the global burden of cardiovascular diseases.