Cardiovascular-kidney-metabolic (CKM) syndrome is a complex and interrelated pathological condition of cardiovascular, renal, and metabolic systems wherein dysfunction in one system precipitates and exacerbates impairments in the others. Due to its increasing incidence and its major impact on morbidity and mortality, the effective treatment of CKM syndrome requires an integrated and interdisciplinary approach. Steps taken to prevent CVD across the lifespan—ranging from early-life nutritional interventions to organized early identification and proper risk profiling to long-term surveillance—are crucial in attenuating disease progression and the occurrence of major adverse clinical events. Management of CKM syndrome involves contemporary drug therapy like sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and nonsteroidal mineralocorticoid receptor antagonists, as well as lifestyle optimization through evidence-based diets. New forms of therapy at the molecular level are promising approaches for intervention on fundamental pathogenic mechanisms. At the same time, the reform of healthcare systems is necessary to promote the expansion of a multidisciplinary approach, equitable access to innovative therapies, and the incorporation of digital technologies for proactive and personalized patient surveillance. In conclusion, optimal patient-centered management of CKM syndromes requires a holistic approach that involves both therapeutic innovation and clinical alignment with population health, with a specific focus on prevention and precision of care.