In the absence of disease impacting the coronary arteries or myocardium, there exists a linear relationship between vessel volume and myocardial mass to ensure balanced distribution of blood supply. This balance may be disturbed in diseases of either the coronary artery tree, the myocardium, or both. However, in contemporary evaluation the coronary artery anatomy and myocardium are assessed separately. Recently the coronary lumen volume to myocardial mass ratio (V/M), measured noninvasively using coronary computed tomography angiography (CTCA), has emerged as an integrated measure of myocardial blood supply and demand in vivo. This has the potential to yield new insights into diseases where this balance is altered, thus impacting clinical diagnoses and management. In this review, we outline the scientific methodology underpinning CTCA-derived measurement of V/M. We describe recent studies describing alterations in V/M across a range of cardiovascular conditions, including coronary artery disease, cardiomyopathies and coronary microvascular dysfunction. Lastly, we highlight areas of unmet research need and future directions, where V/M may further enhance our understanding of the pathophysiology of cardiovascular disease.