A 20-year-old male with fever, myalgia, and jaundice developed severe liver dysfunction, progressing to acute liver failure (ALF). Initial treatment for malaria and supportive care did not resolve symptoms, with persistent jaundice and elevated liver enzymes. Laboratory tests confirmed Plasmodium falciparum/Plasmodium vivax infection. Further evaluation revealed drug-induced liver injury (DILI) from prescribed medications and possible hepatotoxic effects of herbal supplements. Hepatitis A, exacerbated by malaria, DILI, and herbal toxicity, contributed to compounded hepatic dysfunction. Management included intravenous fluids, hepatoprotective agents, and antipyretics. This case underscores the importance of considering multiple etiologies, including infections, drug toxicity, and environmental factors, in ALF.
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