BACKGROUND Cancer is the second leading cause of death internationally, resulting in millions of deaths each year. While treatment in the past has heavily relied on surgery and radiotherapy, chemotherapy and immunotherapy are being increasingly utilized depending on disease presentation. CASE REPORT A 56-year-old male presented to the Emergency Department with a 3-week history of a rapidly enlarging left supraclavicular neck mass. Computed tomography scan revealed a 12×13 cm mass extending from the angle of the mandible to the supraclavicular area. A biopsy confirmed advanced stage squamous cell carcinoma of the head and neck. The patient was started on a chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TCF). The tumor progressed through chemotherapy, which was switched to cetuximab; however, this therapy was discontinued after an anaphylactic reaction. Palliative radiation treatment was begun along with pembrolizumab. Pembrolizumab was continued, and after 9 cycles, the patient's cancer was almost in complete remission. Three months later, disease progression was once again noted with pembrolizumab treatment, which was subsequently discontinued. The patient was started on paclitaxel and carboplatin chemotherapy regimen as a last resort, despite failure of prior TCF treatment, and the patient responded, this time with complete remission in 4 months. CONCLUSIONS This case demonstrates a unique outcome in which a patient who previously was resistant to chemotherapy, later responded to chemotherapy after a trial of radiation therapy and immunotherapy. Immunotherapy may have a synergistic effect with radiation therapy and play a role in tumor sensitivity to chemotherapy in head and neck cancer treatment.