Nasopharyngeal carcinoma (NPC) represents an Epstein-Barr virus (EBV)-associated malignancy showing elevated incidence in East and Southeast Asia. Early detection remains vital, as molecular abnormalities precede visible histological changes during tumor development. This review summarizes recent progress in decoding NPC’s molecular profile, including genetic mutations, epigenetic alterations, non-coding RNA networks, and proteomic alterations. Importantly, these molecular discoveries are increasingly informing clinical approaches to disease management. Modern diagnostic strategies combine histopathological evaluation, EBV DNA/antibodies detection, and imaging technologies. However, locoregional recurrence and distant metastases continue to dominate as primary causes of NPC-related deaths. Immunotherapy has demonstrated growing potential for treating recurrent/metastatic NPC, showing encouraging clinical translation prospects.