Chordoma is a rare malignant tumor with a higher incidence in males than in females. There is an increasing number of clinical studies related to tyrosine kinase inhibitors (TKIs), yet the efficacy and safety of different drugs vary. In this single-arm meta-analysis evaluating the efficacy and safety of TKIs for chordoma treatment, 12 studies involving 365 patients were analyzed. The findings suggest that TKIs can improve outcomes, with an objective response rate of 1.7% and 29% based on RECIST and Choi criteria, a median progression-free survival (mPFS) of 8.41 months and a median overall survival (mOS) of 36.6 months. Imatinib, in particular, showed a longer mOS of 39.3 months compared to 25.0 months for other TKIs. However, high toxicity was noted, with a 95% overall incidence of adverse events (AEs), including hypertension, nausea and vomiting, and edema. Serious AEs occurred at a rate of 55%. In subgroup analysis, Imatinib showed a lower incidence of AEs compared to other TKIs. Combination therapy reduced the risk of severe adverse events compared to monotherapy. The study underscores the potential of TKIs to extend survival in chordoma patients but also highlights the need for careful management of treatment-related toxicity. Combining TKIs, especially imatinib, with other treatments may avoid serious adverse events. Further high-quality clinical trials are needed to confirm these findings and optimize treatment protocols.