Heart failure (HF) remains prevalent in patients who survived myocardial infarction (MI). Despite the accessibility of the primary percutaneous coronary intervention and medications that alleviate ventricular remodeling with functional improvement, there is an urgent need for clinicians and basic scientists to further reveal the mechanisms behind post‐MI HF as well as investigate earlier and more efficient treatment after MI. Growing numbers of studies have highlighted the crucial role of macrophages in cardiac repair and remodeling following MI, and timely intervention targeting the immune response via macrophages may represent a promising therapeutic avenue. Recently, technology such as single‐cell sequencing has provided us with an updated and in‐depth understanding of the role of macrophages in MI. Meanwhile, the development of biomaterials has made it possible for macrophage‐targeted therapy. Thus, an overall and thorough understanding of the role of macrophages in post‐MI HF and the current development status of macrophage‐based therapy will assist in the further study and development of macrophage‐targeted treatment for post‐infarction cardiac remodeling. This review synthesizes the spatiotemporal dynamics, function, mechanism and signaling of macrophages in the process of HF after MI, as well as discusses the emerging bio‐materials and possible therapeutic agents targeting macrophages for post‐MI HF.