A 19-year-old male with second relapsed AML, with initial relapse in the bone marrow and myeloid sarcoma in the cerebellar vermis requiring a total of 5 lines of therapy including allogeneic HSCT, presented with a second relapse isolated to the central nervous system (CNS) as suprasellar myeloid sarcoma two years after initial diagnosis. He received 2 cycles of venetoclax in combination with cytarabine in addition to focal radiation to a total of 24Gy. Despite bacterial and fungal prophylaxis with levofloxacin and micafungin, respectively, his course was complicated by multiple infections, including pulmonary infection with Aspergillus, Gram negative rod sepsis secondary to Klebsiella, additional distinct episodes of bacteremia secondary to Morganella, Staphylococcus epidermidis, and Actinomyces bacteremia, cytomegalovirus (CMV) viremia, a pilonidal abscess, and incidentally discovered appendicitis. Venetoclax was discontinued due to ongoing infections and was not restarted even after resolution of the infections due to persistent pancytopenia with severe thrombocytopenia. The patient developed concern for progressive CNS disease with a new lesion in the right medulla 7 months after initiation of venetoclax therapy, though subsequent imaging improved without intervention, raising the possibility of radiation necrosis or infection. He remains alive with unclear disease recurrence 9 months following initiation of venetoclax.