This review article extensively explores the influence of NF-κB1 gene polymorphism on a diverse range of health issues. The NF-κB pathway, a crucial controller of immune response, is closely associated with numerous disease mechanisms. The NF-kB1 gene has undergone significant genetic changes, and these changes have shown strong connections with the onset and development of numerous disorders. This article investigates the intricate relationship between mutations in the NF-kB1 gene and a wide range of disorders through a thorough study of the literature. These conditions encompass inflammatory disorders, cancer, cardiovascular diseases (CVD), and various other medical ailments. The notable discoveries emphasized within this review underscore the essential role of NF-κB1 gene polymorphism in the development of a range of diseases. Furthermore, these discoveries have important ramifications that could help develop more specialized, successful treatment approaches. To sum up, this work sheds light on the different ways in which NF-kB1 gene variation influences the progression of disorders and highlights the urgent need for more research in this area.