This project investigates myocardial tissue proteomic remodeling associated with cardiac magnetic resonance-defined late gadolinium enhancement burden in patients with hypertrophic cardiomyopathy. Myocardial tissue samples were obtained from patients undergoing septal myectomy, and protein abundance profiles were generated using data-independent acquisition liquid chromatography–tandem mass spectrometry. Quantitative LGE burden was measured as the percentage of left ventricular mass using a 6-SD threshold. Proteome-wide association analysis, pathway enrichment analysis, module score construction, and exploratory mediation analysis were performed to identify myocardial molecular programs associated with increasing LGE burden. The study identified coordinated proteomic alterations involving mitochondrial/oxidoreductive dysfunction, complement-mediated inflammatory activation, and nuclear–cytoskeletal–junctional remodelling.