Drug-induced systemic vasculitis (DISV) is an important and often underrecognized subset of vasculitic syndromes triggered by exposure to various pharmacological agents. Representing approximately 10-20% of vasculitis cases, DISV primarily affects small to medium-sized vessels and can manifest with a wide spectrum of cutaneous and systemic features. The pathogenesis involves complex immunological mechanisms, including hypersensitivity reactions, immune complex deposition, and direct endothelial injury, with emerging evidence of non-classical pathways contributing to refractory disease. Diagnosis relies on a high index of suspicion, detailed drug history, serological testing, and histopathological confirmation. Management centers on prompt withdrawal of the offending drug, supplemented by immunosuppressive therapy in severe or refractory cases. Prognosis is generally favorable with early intervention, but systemic involvement can lead to significant morbidity. This review synthesizes current knowledge on DISV, highlighting epidemiology, pathophysiology, clinical presentation, diagnostic challenges, therapeutic strategies, and future research directions.