The Unani System of Medicine, also referred to as Graeco-Arabic Medicine or Unani Tibb, represents one of the world’s oldest and most enduring traditional medical systems, with a documented history spanning approximately 2,500–2,700 years. Rooted in the humoral theories of ancient Greece as articulated by Hippocrates (460–377 BC) and Claudius Galenus (129–210 AD), and subsequently enriched by the intellectual contributions of eminent Arabian and Persian scholars — most notably Ibn Sina (Avicenna, 980–1037 AD), Muhammad ibn Zakariya al-Razi (854–932 AD), Abu al-Qasim al-Zahrawi (936–1013 AD), and Ibn Nafis (1213–1288 AD) this system has evolved into a holistic and comprehensive framework for the diagnosis, prevention, and treatment of disease. The theoretical architecture of Unani medicine is based on the doctrine of seven fundamental physiological principles (al-Umoor al-Tabiyah), the concept of four humours (Akhlat), the framework of temperament (Mizaj), and the six essential prerequisites of health (Asbab-e-Sitta-e-Zarooriya). Unani pharmacopoeia encompasses more than 2,000 medicinal substances derived approximately 90% from herbal, 4–5% from animal, and 5–6% from mineral sources. The therapeutic modalities of Unani medicine,Ilaj-bil-Tadbeer (regimental therapy), Ilaj-bil-Dawa (pharmacotherapy), and Ilaj-bil-Yad (surgery) reflect a sophisticated, evidence-informed approach to restoring homeostasis. This review provides a detailed, critical synthesis of the historical evolution, doctrinal foundations, pharmacological principles, pharmacovigilance dimensions, and contemporary relevance of the Unani system, drawing upon classical textual sources and recent peer-reviewed literature. The paper also identifies current challenges and opportunities for integrating Unani medicine within modern evidence-based healthcare frameworks.