Abstract: Cardiac resident macrophages (MΦs) play critical roles in maintaining cardiac homeostasis. MΦs participate in and dominate inflammatory responses, tissue repair, and ventricular remodeling following myocardial infarction (MI). Infarct MΦs exhibit remarkable subset heterogeneity, functional diversity, and spatiotemporal specificity in response to dynamically changing microenvironmental stimuli. Therapeutic strategies targeting chemotactic recruitment of inflammatory monocytes/MΦs, specifically inhibiting pro-inflammatory MΦ polarization, and enhancing reparative MΦ functions through metabolic reprogramming have been shown to mitigate post-MI inflammation and improve tissue repair. However, broad-spectrum depletion of MΦs disrupts infarct healing, underscoring their indispensable role in tissue repair. Future studies should further elucidate the molecular basis of phenotypic and functional heterogeneity of infarct MΦs. Developing spatiotemporally specific interventions via genetically engineered MΦs and epigenetic regulation may provide novel therapeutic insights and targets to improve infarct repair by targeting MΦ dynamics.