Azathioprine (AZA) has been extensively used for immunomodulatory effects in autoimmune disorders and transplantation. This article is proposed to review the contemporary and prospective use of AZA in viral, rheumatic, and dermatological disorders. The primary objective is to draw attention to possible developments in regards to AZA application in recent years, with an emphasis on the use of pharmacogenomics and nanotechnology to improve its efficacy in practice. This study reveals that AZA, having the active metabolites 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), may be useful in the treatment of systemic lupus erythematosus (SLE), pemphigus vulgaris, and psoriasis. Pharmacogenomic testing of thiopurine methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) genotypes minimizes the occurrence of myelosuppression. Furthermore, new formulations of AZA using biocompatible polymers and nanoparticles for drug delivery were reported to improve its efficacy and lower systemic toxicity. This paper aims to establish the multifunctional nature of AZA in modern medicine, thus emphasizing its potential for other applications. Through the combination of pharmacogenomic analysis along with nanotechnology application, AZA makes the promise of enhancing patients' treatment efficacy and extending the stock of medical information available. These advancements offer new possibilities for application of precision medicine and improvements in the use of AZA therapy.