Despite substantial advancements in global antiretroviral scaling, Human Immunodeficiency Virus (HIV) remains a critical public health challenge in Nigeria. Holding the second-largest HIV burden in West and Central Africa, Nigeria possesses an estimated 1.9 million people living with HIV (PLHIV) and an adult prevalence rate of 1.3%. This paper reviews the contemporary epidemiological landscape of HIV in Nigeria, delineates its cellular pathophysiology, evaluates current biomedical and structural interventions—including Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP)—and highlights systemic barriers such as social stigma and financing constraints. By aligning data-driven interventions with the structural requirements of vulnerable subgroups, Nigeria can bridge implementation gaps and progress toward the UNAIDS 95-95-95 targets.