The review by You-Lin Tain and Chien-Ning Hsu explores the role of the renin-angiotensin system (RAS) in the development of cardiovascular, kidney, and metabolic (CKM) syndrome, particularly during early life. The RAS plays a crucial role in maintaining homeostasis in various organs, but its dysregulation during pregnancy and lactation can lead to CKM characteristics in offspring. The authors highlight the multi-organ effects of RAS, which influence fetal programming and trigger CKM traits. They discuss interventions targeting the RAS to prevent CKM traits, including renin inhibitors, ACE inhibitors, ARBs, AT1R antisense, and ACE2 activators. While these interventions show promise, more research is needed to optimize their reprogramming effects and determine the optimal therapeutic windows. The review emphasizes the importance of early-life interventions to mitigate the global burden of CKM syndrome.The review by You-Lin Tain and Chien-Ning Hsu explores the role of the renin-angiotensin system (RAS) in the development of cardiovascular, kidney, and metabolic (CKM) syndrome, particularly during early life. The RAS plays a crucial role in maintaining homeostasis in various organs, but its dysregulation during pregnancy and lactation can lead to CKM characteristics in offspring. The authors highlight the multi-organ effects of RAS, which influence fetal programming and trigger CKM traits. They discuss interventions targeting the RAS to prevent CKM traits, including renin inhibitors, ACE inhibitors, ARBs, AT1R antisense, and ACE2 activators. While these interventions show promise, more research is needed to optimize their reprogramming effects and determine the optimal therapeutic windows. The review emphasizes the importance of early-life interventions to mitigate the global burden of CKM syndrome.