The cardiac interstitium is a multifaceted network comprising cells, extracellular matrix (ECM), and signaling molecules that play a critical role in maintaining heart function and facilitating repair mechanisms. This review elucidates the structural composition of the cardiac interstitium, its influence on heart function, and its responses to injury. Recent advancements have highlighted the interstitium active role in modulating mechanical and biochemical signals vital for cardiac function. Key components such as fibroblasts, myofibroblasts, immune cells, and ECM proteins collaborate to sustain the heart's structural integrity and adaptive responses. In the context of cardiac injury, such as myocardial infarction, the interstitium governs processes like inflammation, tissue remodeling, and repair, with dysregulation potentially leading to adverse outcomes like heart failure. This review explores the therapeutic potential of targeting the cardiac interstitium, providing insights into innovative treatments aimed at enhancing cardiac repair and function. By integrating recent research findings, the review aims to offer a comprehensive understanding of the cardiac interstitium role in both health and disease, paving the way for novel therapeutic strategies for heart disease..