Cardiovascular–kidney–metabolic (CKM) syndrome reflects an integrated pathophysiological state where kidney dysfunction plays a central role in amplifying cardiovascular and metabolic risk. This chapter explores the contribution of the kidney to CKM syndrome, emphasizing molecular and systemic mechanisms that promote disease progression. Chronic kidney disease (CKD) is associated with a pro-inflammatory and oxidative environment, contributes to endothelial dysfunction, and leads to neurohormonal imbalance. The pathogenesis is further influenced by comorbid obesity, where immunometabolic activation of adipose tissue exacerbates systemic injury. CKD amplifies cardiovascular morbidity through various pathways, including fluid overload, anemia, and persistent low-grade inflammation. Therapeutic strategies such as renin–angiotensin–aldosterone system inhibitors, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists provide protective effects on kidney and cardiovascular outcomes that extend beyond their roles in lowering blood glucose and blood pressure. Preventive strategies targeting early risk modification and volume control are important for improving outcomes. This chapter presents current evidence on the central role of the kidney in CKM syndrome, emphasizing its contribution to disease progression and outlining therapeutic strategies with renal and cardiovascular benefits.