Obesity and metabolic syndrome (MetS) are some of the most impactful comorbidities frequently encountered in cardiovascular and renal disease. The promotion of unhealthy patterns, driven by the absence of food regulations, lack of proper population education, or financial distress, increases the incidence and prevalence of obesity. Overweight and obese individuals often have associated components of MetS and are more prone to develop cardiovascular disease (CVD), diabetes, metabolic liver disease, or renal disease. Obesity and its forms, specifically visceral fat disposition, through adipokine release and various oxidative and pro-inflammatory pathways, raise the risk of local vascular and tissue damage. Adipose tissue also increases the risk of hypertension with hemodynamic central or peripheric effects that promote renin–angiotensin–aldosterone system (RAAS) activation, endothelial dysfunction, and vascular impairment, with subsequent CVD or chronic kidney disease (CKD). The plethora of mechanisms is complex and intricate; nonetheless, years of research highlight the beneficial effects of weight loss in disease prevention and treatment.