Autoimmune diseases are conditions in which the immune system mistakenly attacks the body’s own tissues. Normally, the immune system defends the body against harmful invaders like bacteria and viruses. However, in autoimmune diseases, the immune system incorrectly identifies certain parts of the body as threats and mounts an attack against them. The most prevalent immunological sign of autoimmune disease is the production of autoantibodies, which provide helpful biomarkers for disease activity, diagnosis, and classification. Among chronic inflammatory autoimmune diseases, RA is the most prevalent and has a complicated pathogenesis. Although the precise cause of RA is still unknown, environmental variables that may cause the disease as well as genetic variations that raise the likelihood of autoimmunity are most likely to be to blame. Joint pain, swelling, stiffness, and loss of function are the primary signs of RA. Traditional RA therapeutic methods offer symptomatic pain and inflammatory alleviation, but they also have systemic side effects. This has led to current research areas that focus on employing nanotechnology to manage RA. The development of nanotechnology has led to the adoption of more and more nano-drugs in the treatment of RA because of the unique physical and chemical properties of nanomaterials. RA can be treated with nanomaterials that selectively target damaged joint tissue and increase bioavailability. The pathogenesis of RA and its treatment with targeted next-generation nanoparticles (NPs) are discussed in this chapter.