Background: Disseminated fusarium, primarily affecting immunocompromised individuals, is associated with persistent fevers, rash, and lung involvement. Despite interventions, mortality rate remains high, exceeding 75% for disseminated disease. There are only 26 documented cases worldwide between 1974 and 2022 with CNS involvement. This case highlights a rare presentation of disseminated fusarium infection involving the lungs, liver, and brain in a 53-year-old male with acute promyelocytic leukemia (APL), highlighting critical diagnostic and therapeutic challenges. Case Presentation: A 53-year-old male with a history of APL with PML/RARA fusion t (15,17) after chemotherapy presented with persistent fevers, rash, encephalopathy, and severe sepsis while undergoing rehabilitation. Initial blood cultures were negative and urine culture was positive for multi-drug resistant enterobacter, for which meropenem was initiated. CT of the chest and abdomen revealed bilateral pulmonary nodules, liver cystic lesions, and signs of cholecystitis. Liver biopsy confirmed fusarium species, prompting treatment with voriconazole monotherapy. Despite surgical intervention and aggressive therapy, the patient experienced worsening respiratory failure, neurological decline, and ultimately transitioned to hospice care where they subsequently passed away. Treatment Approach: Disseminated fusariosis predominantly affects immunocompromised patients, presenting with prolonged febrile illness and cutaneous lesions. MRI head was performed due to acute encephalopathy and showed punctate acute versus subacute infarct in the posterior right cerebellum, small multifocal regions of periventricular/subependymal irregularities and trace fluid within fourth ventricle which correlates to ventriculitis. Infectious disease team added amphotericin B and decreased the voriconazole dose due to worsening of encephalopathy and hallucinations. The case demonstrated resistance to standard therapy, necessitating combination antifungal treatment. Patient’s hospital course was also complicated by gangrenous cholecystitis, which required surgical intervention and additional antibiotics for intra-abdominal infection. Conclusion: This case underscores the critical need for proactive diagnostics with a presentation of immunocompromised status, persistent fevers, disseminated rash, respiratory distress and encephalopathy. Tailored early antifungal regimens and preventative measures are crucial for high-risk patients. The efficacy of combination therapies and advanced imaging techniques in monitoring fusariosis progression, particularly with rare organ involvement such as the liver and brain, should be investigated.