Cardiovascular diseases (CVDs) remain a leading cause of global mortality, with chronic inflammation and irreversible fibrosis being key underlying pathophysiological causes. Cardiac macrophages, as central regulatory players, have garnered significant attention in therapeutic interventions. This review covers advancements in macrophage-centric treatment plans for various CVDs, including myocardial infarction (MI), arrhythmia, and atherosclerosis. It examines the potential consequences and challenges of employing macrophage-targeted techniques, such as modulating macrophage phenotypes, gene therapy, and cell therapy. The review highlights the dynamic activation status of macrophages in different disease contexts and their roles in inflammation, fibrosis, cardiac repair, and regeneration. It also discusses the therapeutic potential of strategies aimed at promoting the transition of macrophages from pro-inflammatory to anti-inflammatory states, which can help mitigate chronic inflammation and hinder heart failure progression. Additionally, the review explores the specific subpopulations of macrophages and their functions in atherosclerosis, ischemic heart disease, and heart failure with preserved ejection fraction (HFpEF). Finally, it reviews current status and challenges of macrophage-targeting strategies, including depletion of monocytes/macrophages, induction of macrophage autophagy, and modulation of adipose tissue macrophages (ATMs).Cardiovascular diseases (CVDs) remain a leading cause of global mortality, with chronic inflammation and irreversible fibrosis being key underlying pathophysiological causes. Cardiac macrophages, as central regulatory players, have garnered significant attention in therapeutic interventions. This review covers advancements in macrophage-centric treatment plans for various CVDs, including myocardial infarction (MI), arrhythmia, and atherosclerosis. It examines the potential consequences and challenges of employing macrophage-targeted techniques, such as modulating macrophage phenotypes, gene therapy, and cell therapy. The review highlights the dynamic activation status of macrophages in different disease contexts and their roles in inflammation, fibrosis, cardiac repair, and regeneration. It also discusses the therapeutic potential of strategies aimed at promoting the transition of macrophages from pro-inflammatory to anti-inflammatory states, which can help mitigate chronic inflammation and hinder heart failure progression. Additionally, the review explores the specific subpopulations of macrophages and their functions in atherosclerosis, ischemic heart disease, and heart failure with preserved ejection fraction (HFpEF). Finally, it reviews current status and challenges of macrophage-targeting strategies, including depletion of monocytes/macrophages, induction of macrophage autophagy, and modulation of adipose tissue macrophages (ATMs).