HIV/AIDS remains a significant public health concern in Johannesburg, South Africa, particularly among female sex workers who are at high risk of infection. A mixed-methods approach combining quantitative surveys with qualitative interviews to gather data on preventive measures and their outcomes among this population. Prevalence rates indicate a substantial risk, with approximately 25% of participants reporting recent HIV infections. Intervention success varied significantly, with some programmes showing efficacy in reducing infection rates by up to 30%. The analysis highlights the need for tailored interventions and continuous monitoring to improve prevention strategies targeting female sex workers in Johannesburg. Implement evidence-based, culturally sensitive HIV/AIDS prevention programmes that include regular health screenings, education on safe practices, and access to antiretroviral therapy (ART).