Background: Classical Indian medicine underwent a paradigm shift during the early medieval period with the formal integration of Rasa Shastra (Indian iatrochemistry and alchemy). Attributed historically to the polymath and Siddha philosopher Acharya Nagarjuna, this discipline bridged the pursuit of transmutational metallurgy (Dhatuvada) with internal rejuvenation and clinical therapeutics (Dehavada). Methods: This historical-analytical paper investigates classical Sanskrit treatises, primarily the Rasaratnakara, Rasendramangala, and relevant chapters of the Charaka and Sushruta Samhitas, alongside contemporary historical, chemical, and pharmacological scholarship. Comparative textual synthesis, historical contextualization, and metallurgical assessment were conducted to trace the philosophical and operational evolution of Nagarjuna’s contributions. Results: Nagarjuna systematized the eighteen pharmaceutical processing operations (Ashtadasha Samskara) of Parada (mercury), engineered early distillation and heating apparatuses (Yantras), and conceptualized processes such as Shodhana (purification), Marana (calcination), and Jarana (assimilation). These techniques converted toxic heavy metals into stable, bioavailable organo-metallic complexes (Bhasmas). Conclusion: Nagarjuna did not treat alchemy as a speculative pursuit of base wealth, but as an empirical science where metallurgical mastery served as the laboratory validation for biological immortality and rapid therapeutic intervention. Rasa Shastra represents one of the earliest systematized traditions of applied materials science and nanomedicine.