Background: Advanced Human Immunodeficiency Virus Disease (AHD) is an important public health issue, especially in resource-constrained settings like Western Nigeria. Understanding the socio-demographic and clinical factors influencing AHD is essential for developing targeted interventions to mitigate its impact. Objective: To identify socio-demographic and clinical predictors of AHD in HIV-positive patients and explore their implications for disease management in a low-resource healthcare setting. Methods: A cross-sectional study was conducted using archived clinical and laboratory data from the Public Health Laboratory, State of Osun Hospitals Management Board, Ede, Nigeria. Data included socio-demographics, clinical characteristics, CD4 counts, and viral loads of HIV-positive patients between February 2023 and March 2024. Descriptive statistics summarized key variables, and chi-squared tests analyzed associations between socio-demographic factors and AHD. Results: The study included 110 participants, 55.5% of whom had AHD. Significant predictors of AHD included age (p=0.007), duration of illness (p=0.002), transmission route (p=0.026), daily income (p<0.001), and educational status (p=0.001). Notably, lower income (<$1 daily) and lack of formal education were strongly associated with AHD prevalence. The predominant transmission route was heterosexual contact (68.2%), and long-term illness significantly increased AHD risk. Conclusion: Socio-economic and clinical disparities play pivotal roles in the progression to AHD in Western Nigeria. Addressing these factors through comprehensive medical, educational, and socio-economic interventions is vital for improving health outcomes among people living with HIV. Further research should explore longitudinal trends and intervention efficacy.