The cardiovascular–kidney–metabolic (CKM) syndrome has a systemic impact, contributing to the appearance of clinical and biological manifestations that influence the quality of life of these patients. The pathophysiological mechanisms underlying CKM lead to the appearance of a hypercoagulable state—an acquired form of thrombophilia—as well as an anemic syndrome. Thromboembolic disease and ischemic stroke are frequently associated with increased mortality and morbidity, which is why knowledge of the mechanisms that lead to their occurrence in CKM is essential to correctly assess the thrombotic risk to establish appropriate management. Anemia is a major health problem that is often associated with metabolic syndrome (obesity, diabetes mellitus), chronic kidney disease, and cardiovascular diseases. Therefore, this chapter focuses on the epidemiological, pathophysiological, clinical, and paraclinical details of these two clinical entities. The hematological impact is described, especially its impact on vascular endothelium, fluid-coagulant system, megakaryocyte, and the erythrocyte series. Starting from the objective evidence that demonstrates the increased risk of thrombosis in CKM syndrome, the use of tools to assess thrombotic risk becomes a necessity in current clinical practice. This chapter focuses on identifying the main algorithms that assess thrombotic risk and their therapeutic particularities. The management of these patients with hypercoagulable status and anemic syndrome in the context of CKM syndrome most often requires a multidisciplinary approach.