The benefits of breastfeeding for both mother and infant are generally recognized; however, the connections between breast milk, lactation, and long-term offspring health and disease remain incompletely understood. Cardiovascular-kidney-metabolic syndrome (CKMS) has become a major global public health challenge. Insufficient breast milk supply, combined with various early-life environmental factors, markedly increases the future risk of CKMS, as highlighted by the developmental origins of health and disease (DOHaD) concept. Given its richness in nutrients and bioactive components essential for infant health, this review focuses on reprogramming strategies involving breast milk to improve offspring's cardiovascular, kidney, and metabolic health. It also highlights recent experimental advances in understanding the mechanisms driving CKMS programming. Cumulatively, the evidence suggests that lactational impairment heightens the risk of CKMS development. In contrast, early interventions during the lactation period focused on animal models that leverage breast milk components in response to early-life cues show potential in improving cardiovascular, kidney, and metabolic outcomes-an area warranting further investigation and clinical translation.