In this comprehensive lecture, Dr. Lee, Chi-Ho Paul reframes obesity as a chronic, complex disease and a central driver of cardiovascular-kidney-metabolic (CKM) syndrome. Beyond conventional body mass index (BMI)-based definitions, emphasis is placed on confirming excess adiposity and distinguishing preclinical from clinical obesity to enable risk-based, goal-directed management. The pathophysiology linking dysfunctional adipose tissue to inflammation, insulin resistance, and end-organ damage is outlined, highlighting why durable weight control is physiologically challenging and often requires long-term pharmacotherapy. Emerging evidence highlights the transformative role of dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonists, which deliver significant and sustained weight reduction alongside improvements in glycemic control, cardiovascular risk, renal outcomes, and obesity-related complications such as obstructive sleep apnoea (OSA) and metabolic dysfunction-associated steatohepatitis (MASH). The lecture underscores a shift toward precision, long-term obesity management, with dual receptor agonism positioned as a key therapeutic advancement in optimizing CKM health.