Background <p>Therapeutic options for patients with poor-prognosis invasive triple-negative breast cancer (TNBC) remain lacking. Although novel treatment strategies have demonstrated improved efficacy, they are frequently associated with substantial financial costs. Consequently, rigorous economic evaluation is essential to inform clinical and policy decisions.</p> Methods <p>A three-state Markov model with a lifetime horizon was developed using clinical efficacy data from the ASCENT-04/KEYNOTE-D19 trial, along with treatment-related cost inputs. Lifetime costs and health outcomes in cases of advanced TNBC for patients undergoing treatment with either sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab were estimated with the developed model. Model uncertainty and structural stability were examined via probabilistic and deterministic sensitivity analyses. Total costs, quality-adjusted life-years (QALYs), incremental net health benefit (INHB), incremental net monetary benefit (INMB), and incremental cost-effectiveness ratios (ICERs) were examined at a willingness-to-pay (WTP) threshold of $150,000/QALY in the USA.</p> Results <p>The estimated lifetime cost was $1,831,187 for sacituzumab govitecan plus pembrolizumab and $574,011 for chemotherapy plus pembrolizumab. Corresponding health outcomes were 5.28 QALYs and 4.74 QALYs, respectively. The resulting ICER was $2,323,487 per QALY gained. The INHB and INMB were -7.84 QALYs and -$1,176,175, respectively. The most influential variables in the model included the utility value assigned to progression-free survival, patient body weight, and the cost-effectivness of sacituzumab govitecan. Sensitivity analysis demonstrated that the model findings were robust.</p> Conclusions <p>At current market prices, sacituzumab govitecan plus pembrolizumab showed limited cost-effectiveness as a first-line option relative to chemotherapy plus pembrolizumab for treating advanced TNBC.</p>