Introduction: Locally advanced thyroid cancer presents significant therapeutic challenges, particularly when tumours exhibit aggressive biology and invade critical structures, rendering them unresectable at presentation. This study evaluates the efficacy of neoadjuvant multikinase inhibitor therapy in enhancing surgical resectability in patients with locally advanced disease. Methods: A retrospective review was conducted on patients with locally advanced, unresectable thyroid cancer treated between January 2017 and December 2022. Multidisciplinary team assessment identified seven patients, of whom five received lenvatinib with three-monthly follow-up. Treatment response was evaluated using RECIST criteria, and outcomes included therapy safety, progression to surgery, and overall survival. Results: Five patients with cT3/T4 disease were treated with neoadjuvant lenvatinib and achieved objective response to treatment with significant reduction in tumour size (mean 30.5 ± 17.4%). Four patients proceeded to surgery achieving a 50% R1 and 50% R2 resection rate. Adverse events were mild or moderate, and resolved with dose reduction or when neoadjuvant therapy was withheld pre-operatively. To date three patients who underwent surgery are alive with a median follow up of 44.7 months (range 30.1-53.3 months), with one death from distant disease 13 months after diagnosis. Conclusion; In this small series, neoadjuvant lenvatinib therapy demonstrated effective antitumour activity in locally advanced thyroid cancer and facilitated surgical resection.