Metabolic syndrome (MetS) is a group of cardio-metabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia; these are also a combination of independent coronary artery disease (CAD) risk factors. Alarmingly, the prevalence of MetS risk factors are increasing and a leading cause for mortality. In the vasculature, complications from MetS and type 2 diabetes (T2D) can be divided into microvascular (retinopathy and nephropathy) and macrovascular (cardiovascular diseases and erectile dysfunction). In addition to vascular and endothelial dysfunction, vascular remodeling and stiffness are also hallmarks of cardiovascular disease (CVD), and well-characterized vascular changes that are observed in the early stages of hypertension, T2D, and obesity [1–3]. In the heart, the link between obstructive atherosclerosis of coronary macrovessels and myocardial ischemia (MI) is well established. However, recent studies show that abnormalities in the coronary microcirculation are associated with functional and structural changes in coronary microvessels (classically defined as being ≤150–200 μm internal diameter), which may cause or contribute to MI even in the absence of obstractive CAD. This suggests a prognostic value of an abnormal coronary microcirculation as an early sub-clinical culprit in the pathogenesis and progression of heart disease in T2D and MetS. The aim of this review is to summarize recent studies investigating the coronary microvascular remodeling in an early pre-atherosclerotic phase of MetS and T2D, and to explore potential mechanisms associated with the timing of coronary microvascular remodeling relative to that of the macrovasculature.