Cardiometabolic disease (CMD) represents the major cause of mortality, accounting for one-third of all global deaths, 75% of which occur in middle- and low-income countries. CMD encompasses a broad spectrum of conditions characterized by limited prediction, based mainly on classical risk factors due to a lack of accurate molecular CMD predictors. Thus, there is an urgent need for improved diagnostics solutions to support early intervention and improve outcomes. Early detection and adequate intervention are crucial to prevent CMD-associated complications, encouraging the quest for appropriate biomarkers with diverse applications ranging from risk assessment and screening to diagnosis and prognosis. Different circulating biomarkers for quantifying the CMD risk have been reported in the literature, such as C-reactive protein (CRP), leptin, and adiponectin. In addition, accumulating evidence in the literature points to the emergence of novel CMD biomarkers, such as cytokines, various metabolites, apelin, microRNAs, inflammasome molecules, and cardiac fibrosis markers. However, large meta-analyses have not sufficiently investigated and confirmed their biological roles in CMD diagnosis, prognosis, and/or potential reduction.