<p>Heart injury after acute myocardial infarction requires adequate repair to prevent left ventricular remodelling and the development of chronic heart failure. The early immune response to myocardial injury and its tight interconnection to fibroblast activation have a crucial role in determining the outcome after myocardial infarction. Emerging therapies aim to exploit these targets, harnessing the subacute window after cardiac injury to prevent subsequent contractile dysfunction. Given the complexity of the tissue response to myocardial injury and the molecular specificity of targeted therapies, only a subgroup of individuals might benefit from these therapies, which emphasizes the need for personalized therapies and the identification of suitable biomarkers to classify patients. Radiotracer-based, non-invasive molecular imaging is rapidly evolving alongside targeted drug development, providing novel tools for the investigation of immune and profibrotic mechanisms. These molecular imaging techniques hold unique potential to guide the development and selection of reparative therapies based on precise information about the most suitable candidates and the timing after acute myocardial infarction. In this Review, we outline a roadmap for the clinical implementation of radiotracer-based molecular imaging of immune and fibrotic pathways to guide targeted therapies for heart repair. The long-term goal is to establish clinical algorithms for immune-targeted and fibrosis-targeted imaging-guided therapy for cardiac repair.</p>