This review synthesizes recent evidence to elucidate how chronic stress promotes carcinogenesis through the bidirectional interaction between the GR and NF‐κB. We have comprehensively detailed how pathological GR modifications, including PTMs and GC resistance, impair GR sensitivity, leading to the disinhibition and hyperactivation of NF‐κB, which in turn drives tumor initiation, proliferation, and metastasis. The gene discussed is NFKB1; the disease is neoplasm.