Background: Systemic therapy for head and neck squamous cell carcinoma (HNSCC) was historically reserved for recurrent or metastatic disease. The advent of immunotherapy has transformed management, with checkpoint inhibitors now standard in advanced disease and increasingly investigated in the neoadjuvant setting, shifting from cytotoxic debulking to immune-priming strategies. Methods: A bibliometric analysis using Web of Science keywords was conducted to map trends in neoadjuvant HNSCC drug research over four decades, focusing on chemotherapy and immunotherapy agents. Results: Two major eras were identified. The cytotoxic era (1990–2015) was dominated by cisplatin and 5-fluorouracil, emphasizing locoregional control and surgical downstaging. The immunotherapy era (2016–2026) showed a marked rise in publications on checkpoint inhibitors, particularly pembrolizumab and nivolumab, expanding from metastatic to neoadjuvant contexts and peaking around 2025. Although cisplatin remains the most studied agent overall (n=137), recent growth is driven by immunotherapy. Pembrolizumab publications increased nearly fourfold from 2021 to 2025. Interest in combination chemoimmunotherapy and newer agents such as durvalumab and avelumab is also rising, reflecting attempts to enhance synergistic antitumour effects. Conclusion: Current literature highlights a paradigm shift toward immune priming in the preoperative window to induce durable systemic immunity. Neoadjuvant strategies are evolving beyond tumour downstaging to biologically driven treatment approaches. For surgical oncologists, immunotherapy is rapidly becoming central to neoadjuvant research and is likely to shape future standards of care in locally advanced HNSCC.