The association between obesity, type 2 Diabetes Mellitus (DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) is increasingly and widely recognized in developed countries. This condition has been collectively defined by the American Heart Association (AHA) as the Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is characterized by hyperglycemia, insulin resistance, and increased activity of the renin-angiotensin-aldosterone system (RAAS), formation of advanced glycation end products, oxidative stress, lipotoxicity, endoplasmic reticulum stress, abnormal calcium handling, mitochondrial dysfunction and impaired energy production, and chronic inflammation. Addressing their prevention, management, and treatment is of paramount importance to improve patient health outcomes. The aim of this review is to provide a comprehensive overview of the status and new treatment modalities for the recently described CKM syndrome.