Background: The management of asymptomatic cryptococcal antigenemia in pregnant women with advanced human immunodeficiency virus (HIV) disease presents a therapeutic dilemma. Clinicians must balance the risks of vertical transmission, immune reconstitution inflammatory syndrome (IRIS), and antifungal teratogenicity. Case Summary: We report a case of a 28-year-old HIV-positive woman in Kenya who presented at 34 weeks of gestation with symptoms suggestive of meningitis. She had self-discontinued her antiretroviral therapy (ART) 18 months prior. Laboratory investigations confirmed a positive serum cryptococcal antigen (CrAg) with a high HIV viral load (41200 copies/mL). Lumbar puncture ruled out meningeal involvement. A multidisciplinary team initiated preemptive therapy with high-dose fluconazole (800 mg daily). Faced with her advanced gestation and the imperative to prevent perinatal transmission, a calculated risk was taken to initiate ART (tenofovir/lamivudine/dolutegravir) after only 7 days, a significant deviation from standard guidelines. At 36 weeks, she had a spontaneous vaginal delivery complicated by uterine inversion and postpartum hemorrhage, which was managed successfully. She did not develop cryptococcal IRIS. At 3-month follow-up, her viral load was suppressed (51 copies/mL), and her infant was HIV-negative with normal development at 6 months. Conclusions: This case highlights the importance of routine CrAg screening in pregnant women with advanced HIV. Preemptive fluconazole in the third trimester is feasible. The timing of ART initiation may need individualization to prevent vertical transmission in late gestation, particularly in the context of isolated antigenemia, where the IRIS risk profile may differ from cryptococcal meningitis. These decisions require multidisciplinary input and close monitoring.