Metabolic syndrome (MetS) is a multifactorial cluster of cardiometabolic abnormalities, including central obesity, insulin resistance, dyslipidaemia, and hypertension, that significantly elevate the risk for type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and non-alcoholic fatty liver disease (NAFLD). Although traditionally associated with adults, MetS is increasingly prevalent in the adolescent population, paralleling the global surge in childhood obesity. Early onset of MetS carries substantial implications for long-term health, as the condition often tracks into adulthood and is associated with early vascular changes and subclinical organ damage. Understanding MetS in adolescents presents unique challenges. The lack of consensus definitions, physiological changes during puberty, and the need for age, sex, and ethnicity-specific criteria have limited the uniform application of diagnostic thresholds. Furthermore, the syndrome’s pathophysiology involves complex interactions between adipose tissue dysfunction, chronic low-grade inflammation, oxidative stress, genetic predisposition, and environmental factors. This chapter provides a comprehensive synthesis of current knowledge on MetS in adolescents. It explores the historical evolution of the syndrome’s concept, outlines major diagnostic definitions, and highlights epidemiological trends across populations. The chapter delves into pathophysiological mechanisms, clinical manifestations, and associated comorbidities such as polycystic ovary syndrome (PCOS), NAFLD, and sleep-disordered breathing. Special attention is given to inflammatory and oxidative biomarkers, as well as at-risk subpopulations, including ethnic minorities and youth with adverse intrauterine exposures. The aim of this chapter is to inform clinicians, researchers, and policymakers on the urgent need for early recognition, stratified risk assessment, and targeted intervention strategies in adolescents with MetS, thereby improving lifelong cardiometabolic outcomes and reducing global health burden.