By evaluating the molecular and epigenetic patterns and overviewing the link between inflammation markers (CRP, monocytes, leukocytes, neutrophils), gene expression analysis (FTO, YTHDF1, METTL3, IL-1β, IL-8, and TNFα), and global DNA methylation (5-mC), novel personalized therapies could be developed and could address more efficiently the obesity-related inflammatory and metabolic dysfunctions. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.