Cardiovascular-kidney-metabolic syndrome (CKM) represents the intersection between metabolic, renal, and cardiovascular dysfunction. It is characterized by the complex interplay between multiple risk factors. This chapter provides an overview of the epidemiology of CKM syndrome. It focuses on the global prevalence of CKM and how its incidence varies across different age groups, ethnicities, and regions. CKM syndrome is particularly prevalent in populations with a high incidence of obesity, diabetes, hypertension, and an aging population. Advanced stages are more prevalent in men and older adults. Moreover, social determinants of health, such as income or educational status, are also linked with CKM disease progression. Risk factors including hypertension, obesity, high serum glucose, inflammation, or oxidative stress play an important role in exacerbating cardiovascular and renal damage. Moreover, this chapter focuses on the way genetic predisposition and epigenetic modifications and behavior play a role in cardio-renal-metabolic risk. Finally, it is important to recognize the importance of a multidisciplinary approach in managing all stages of CKM, from prevention to mitigation of its consequences.