Ruxolitinib, a selective inhibitor of Janus kinase 1 and 2, has emerged as a pivotal therapeutic agent in the management of myeloproliferative neoplasms, particularly primary myelofibrosis. The JAK-STAT signaling pathway, which is integral to cellular proliferation and differentiation, is effectively modulated by ruxolitinib, leading to significant clinical benefits, such as a reduction in splenomegaly, alleviation of constitutional symptoms, and improved survival outcomes in affected patients. Despite these advantages, the immunosuppressive properties of ruxolitinib raise concerns regarding the heightened risk of opportunistic infections, notably disseminated tuberculosis. The drug’s impact on the immune system manifests through the inhibition of T helper 1 cell functionality and the downregulation of essential cytokines, including interferon-gamma and tumor necrosis factor-alpha, both of which are crucial for the host’s defense against Mycobacterium tuberculosis. This report details the case of a 62-year-old woman with a history of primary myelofibrosis who developed disseminated tuberculosis during her treatment with ruxolitinib. This case highlights the importance of maintaining a high index of suspicion for infectious complications in patients receiving JAK inhibitors. These findings underscore the need for early diagnosis and ongoing clinical vigilance to identify and manage such adverse events effectively. By presenting this case, we aim to contribute to the growing body of literature that highlights the clinical implications of ruxolitinib therapy, particularly regarding its association with serious infectious complications, and to advocate for enhanced monitoring strategies in patients undergoing treatment with this agent.