Cardiovascular-kidney-metabolic (CKM) syndrome is a pathophysiological entity resulting from the intricate interplay between metabolic, renal, and cardiovascular dysfunction. This chapter explores the roles of inflammation and oxidative stress in CKM syndrome and emphasizes how persistent chronic low-grade inflammation and oxidative stress contribute to endothelial dysfunction, atherosclerosis, renal fibrosis, and insulin resistance. The burden of inflammation and oxidative stress is particularly pronounced in patients with obesity, type 2 diabetes, and hypertension, conditions that cluster in ageing populations and are influenced by socioeconomic and environmental factors. In addition to genetic susceptibility and epigenetic influences, lifestyle factors such as poor diet, sedentary behavior, and tobacco exposure intensify oxidative and inflammatory cascades. These interactions create a vicious cycle that perpetuates cardiovascular and kidney injury. Finally, the chapter underscores the importance of targeted therapeutic strategies, including SGLT2 inhibitors and GLP-1 receptor agonists, which exhibit both anti-inflammatory and antioxidant properties. A multidisciplinary approach integrating pharmacologic and behavioral interventions is essential for disrupting these pathogenic pathways and mitigating the long-term consequences of CKM syndrome.