The emerging role of neoadjuvant therapy in the management of locally advanced thyroid cancer marks a significant progress in the field. Recent developments in systemic therapies, particularly with the introduction of multikinase inhibitors and selective inhibitors, have demonstrated promising results. The objective of this review is to delve into the implications of these developments and their potential impact on the management of advanced thyroid cancers which initially present as borderline resectable or unresectable. For DTC and PDTC, agents like lenvatinib have shown substantial tumor reduction, facilitating surgical resection. Similarly, for MTC, selpercatinib have exhibited interesting response rates, enhancing the feasibility of surgery with reduced morbidity in limited clinical case series of patients with RET mutations. In BRAF mutant ATC, the combination of BRAF and MEK inhibitors, has significantly improved treatment protocols, providing a pathway to surgical intervention and significantly improving survival rates. The addition of immune checkpoint inhibitors to these regimens showed further extension of survival and reduced recurrence rates in retrospective studies that still need confirmation. Despite these preliminary favorable results, neoadjuvant therapies are not without challenges. The risk of adverse events, particularly related to the inhibition of the VEGF pathway, necessitates careful patient selection and management. The variability in tumor responses and the potential for serious complications underscore the need for continued research to refine these approaches in this difficult patient population.