Cardiac amyloidosis (CA) represents an emerging challenge in cardiovascular medicine, with notable clinical overlaps and diagnostic complexities when coexisting with coronary artery disease (CAD). This integrative review navigates the intricate terrain of CA and CAD, elucidating epidemiology, clinical presentations, and diagnostic considerations. Examining both immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis, we underscore their shared demographic associations, diagnostic intricacies, and potential diagnostic confounders with CAD. Notably, we emphasize the impact of CA on epicardial coronary arteries and the consequential implications for coronary microcirculation. Further exploration reveals the connection between CA and acute myocardial infarction, emphasizing early recognition as pivotal. In terms of differential diagnosis, we underscore the significance of clinical symptoms, electrocardiography, echocardiography, cardiac magnetic resonance, and bone scintigraphy. Additionally, we scrutinize the intricate realm of treatment, encompassing medication selection, antithrombotic strategies, and revascularization modalities. Our review addresses the distinctive challenges posed by CA patients’ limited tolerance for conventional therapies. This comprehensive synthesis serves as an invaluable resource for clinicians confronting the intricate intersection of CA and CAD. By offering insights into diagnostic refinement and innovative therapeutic avenues, we aim to enhance patient outcomes and quality of life within this complex clinical landscape.