Oropharyngeal cancer (OPC), affecting the tonsils, base of the tongue, and soft palate, has witnessed a notable increase in incidence, particularly among cases linked to human papillomavirus (HPV) infection. This epidemiological shift has led to changes in treatment strategies, with immunotherapy emerging as a promising alternative to conventional modalities such as surgery, radiation, and chemotherapy, which are often associated with significant toxicity. This systematic review aims to evaluate the current landscape of immunotherapeutic interventions in OPC, including immune checkpoint inhibitors, monoclonal antibodies, adoptive T cell therapies, and cancer vaccines. It also explores the influence of HPV status, the development of predictive biomarkers, and the direction of ongoing clinical trials. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science for studies published between 2010 and 2025. Keywords included "oropharyngeal cancer," "HPV," "immunotherapy," "checkpoint inhibitors," "monoclonal antibodies," "cancer vaccines," and "T cell therapy." Eligible peer-reviewed articles, clinical trials, and reviews focusing on immunotherapy for OPC were included. Data were synthesized based on immunotherapy type, HPV status, clinical outcomes, and biomarker relevance. The review highlights substantial evidence supporting immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1) in improving survival and minimizing adverse effects, particularly in HPV-positive patients. Monoclonal antibodies enhance immune targeting of tumor cells, while cancer vaccines and adoptive T cell therapies show encouraging preliminary outcomes. HPV status and emerging biomarkers are critical in predicting responses and guiding patient-specific therapies. Immunotherapy offers a transformative opportunity in OPC management. Ongoing trials and biomarker research are key to advancing personalized treatment strategies.