Purpose <p>Anaplastic thyroid cancer (ATC) is a highly aggressive tumour with a near 100% disease specific mortality. Despite these issues, there exists a lack of a standardised treatment regimen. We present a systematic review and the first ever network meta-analysis discussing a wide range of treatment options, namely surgery, radiotherapy (RT), chemotherapy (CT), tyrosine kinase inhibitors (TKIs) and the various combinations utilised in ATC. Databases PubMed, Embase, Cochrane and Web of Science were systematically searched for relevant literature.</p> Methods <p>A qualitative analysis was conducted following PRISMA guidelines. The primary effect-measure was Hazard Ratios (HRs). A network meta-analysis assessed pairwise comparisons between all combinations of standard treatment (surgery, RT and CT), while a standard meta-analysis evaluated the impact of each modality, including TKI therapy and resection status, on overall survival (OS).</p> Results <p>38 studies were included in our review, 8 in the network meta-analysis and 32 in the standard meta-analyses. The network meta-analysis revealed that CT + RT had an increased OS compared to RT alone. Adding RT into a surgical treatment regimen increased OS, but CT did not. No significant difference in OS was found between trimodality treatment and surgery + RT. Standard meta-analysis indicated that surgery, RT, CT, TKIs, and complete resection (R0) were associated with increased OS.</p> Conclusion <p>Surgery, RT, CT, TKIs and their combinations contribute to prolonged OS in ATC. Despite treatment benefits, the prognosis of ATC remains dismal. Further research is needed to optimise multimodal strategies and explore novel therapeutic approaches, including targeted and immunotherapy options.</p>