While younger and age-matched females consistently demonstrate greater intrinsic cardiac resilience following ischemic injuries compared to males, the underlying systemic and metabolic mechanisms driving these differences remain poorly understood. Acute ischemic insults, such as a myocardial infarction (MI), trigger severe decrements in cardiac output and initiate extensive structural and functional remodeling. This future research initiative will utilize an integrative, Guytonian approach to quantify how sex-specific regulatory nodes and metabolic switches dictate whether a heart adapts or lapses into maladaptive failure.