We provide evidence of the existence of the cardiometabolically healthy obesity phenotype and highlight the potential of adipokines such as leptin, adiponectin, IL-18, and chemerin; the inflammatory marker hs-CRP; and gut dysbiosis, as indicators of the evolution from the cardiometabolically healthy to the cardiometabolically abnormal phenotype within this population. This evidence concerns the gene RARRES2 and obesity due to melanocortin 4 receptor deficiency.