ObjectiveThis study assessed the cost-effectiveness of pyrotinib combined with trastuzumab and docetaxel as a first-line treatment for HER2-positive metastatic breast cancer from the perspective of the Chinese healthcare system.MethodsA partitioned survival model was constructed to evaluate the cost-effectiveness of this regimen in patients with HER2-positive metastatic breast cancer. The primary outcomes were total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). The treatment strategy was considered cost-effective when the ICER fell below a predefined willingness-to-pay (WTP) threshold. One-way and probabilistic sensitivity analyses were conducted to address parameter uncertainties. Additional scenario analyses were performed to explore how different assumptions influenced the ICER.ResultsIn the base-case analysis, the pyrotinib group incurred total costs of 136,400.69comparedwith136,400.69 compared with 83,887.55 in the placebo group. The corresponding effectiveness was 5.20 QALYs versus 3.89 QALYs. The ICER was 40,245.81/QALY,whichexceededtheWTPthreshold(twotimesChinaspercapitaGDPin2025,40,245.81/QALY, which exceeded the WTP threshold (two times China’s per capita GDP in 2025, 27,906.03/QALY). One-way sensitivity analysis revealed that utility of progression-free survival and the price of pyrotinib were the most influential factors on the ICER. Probabilistic sensitivity analysis indicated that at the WTP threshold of $27,906.03/QALY, pyrotinib had a 6.1% probability of being cost-effective. Scenario analyses confirmed the robustness of the model. Price threshold analysis showed that the price of pyrotinib would need to be reduced by more than 34.45% to bring the ICER below the WTP threshold.ConclusionFrom the Chinese healthcare perspective, pyrotinib combined with trastuzumab and docetaxel may not be cost-effective for HER2-positive metastatic breast cancer under current prices and the WTP threshold. A price reduction would be required to achieve cost-effectiveness.