Progression in understanding the relationships among cardiovascular, kidney, and metabolic diseases necessitates reappraising these concepts. Here, this narrative review explains the evolution of the ideas behind cardiovascular-kidney-metabolic syndrome (CKMS), focusing both on the impact of kidney disease on the cardiovascular system and metabolic syndrome and, conversely, on the effects of metabolic syndrome on cardiovascular and kidney diseases. Merging these concepts has resulted in a holistic approach more pertinent to managing the increased pressure from civilization diseases. In light of recent guidelines, early laboratory assessment is critical for risk stratification by improved patient classification, enabling individualized therapeutic strategies. Moreover, understanding the molecular mechanisms common to these systemic disorders not only enhances diagnostic accuracy but also facilitates the implementation of preventive measures that target multiple organ pathologies simultaneously. This review summarizes selected laboratory parameters that may support the diagnosis and management of cardiovascular-kidney-metabolic syndrome, aligning current knowledge with emerging clinical recommendations.