Refractory thyroid cancer is frequently associated with a poor prognosis, necessitating alternative therapeutic approaches. Tyrosine kinase inhibitors (TKIs) have emerged as a promising treatment option, showing generally favorable clinical outcomes in these challenging cancer subtypes. However, the existing body of research is constrained by small sample sizes and variable findings, limiting the ability to directly compare the efficacy of different TKI agents. This study aimed to bridge that gap through a network meta-analysis, evaluating the relative efficacy and safety of various TKIs in managing refractory thyroid cancer. Utilizing systematic keyword searches in databases such as PubMed, Cochrane Library, Embase, Scopus, Web of Science, and ClinicalTrials.gov, we identified studies that met predefined inclusion criteria. Extracted data were analyzed using Bayesian network meta-analysis methods via R software to ensure a comprehensive assessment. Our findings highlighted specific advantages of certain TKIs for various clinical outcomes. In terms of progression-free survival (PFS), Anlotinib and Apatinib showed notable efficacy. For the objective response rate (ORR), Cabozantinib and Lenvatinib demonstrated superior effectiveness, while for disease control rate (DCR), Apatinib and Lenvatinib were advantageous. Regarding safety profiles, Cabozantinib emerged as the safest option for all-grade adverse events (AEs), with Anlotinib showing a higher risk. For severe AEs (grade 3 or higher), Sorafenib proved to be the safest, while Apatinib carried the highest risk. In summary, Anlotinib, Apatinib, Lenvatinib, and Cabozantinib offered significant benefits for PFS, ORR, and DCR in patients with refractory thyroid cancer. However, Anlotinib and Apatinib were associated with higher AE rates, underlining the importance of balancing efficacy with safety. Cabozantinib and Vandetanib, while exhibiting comparatively safer profiles, showed moderate efficacy. These insights underscored the necessity for tailored treatment decisions that carefully weigh the benefits and risks of each TKI agent.