Background: The human immunodeficiency virus (HIV) primarily targets CD4+ cells, leading to a weakened immune system. Patients in Stage IV HIV are highly susceptible to systemic fungal infections. The prevention of opportunistic fungal infections, early detection, and identification of their risk factors are critical, particularly in advanced HIV cases. Objective: This study seeks to identify the risk factors associated with systemic fungal infections in Stage IV HIV patients at Haji Adam Malik General Hospital, Medan. Methods: This observational analytical study adopted a retrospective approach using the medical records of patients treated at the hospital from 2018 to 2023. The sampling method employed was consecutive sampling. Shapiro-Wilk tests were used for distribution analysis, and bivariate analysis determined the relationship between various risk factors (CD4+, Type 2 Diabetes Mellitus, pulmonary and extrapulmonary tuberculosis, and albumin levels) and systemic fungal infections in HIV Stage IV patients using chi-square tests. Multivariate analysis was performed thereafter. The statistical significance threshold was set at α = 0.05, with p-values less than 0.05 considered statistically significant. Results: The study involved 64 subjects. Systemic fungal infections were most prevalent among patients aged 19 to 44 years, with males being more commonly affected. The mean CD4+ count among Stage IV HIV patients with systemic fungal infections was 43.5 (+ 43.4), while those without such infections had a mean CD4+ count of 82.1 (+57.9). A statistically significant relationship was observed between CD4+ and albumin levels and the incidence of systemic fungal infections (p < 0.05). Multivariate analysis revealed that both low albumin and CD4+ levels were significant risk factors for the development of systemic fungal infections in Stage IV HIV patients. Conclusion: CD4+ and albumin levels are significant risk factors for systemic fungal infections in Stage IV HIV patients.