Purpose <p>Socazolimab, in combination with chemotherapy, has been shown to prolong progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (ES-SCLC). This study is the first to evaluate its cost-effectiveness from the perspectives of both the U.S. payer and Chinese healthcare systems.</p> Methods <p>A Markov state-transition model was employed to conduct an economic evaluation, incorporating clinical and economic parameters from both the U.S. and China. Baseline patient characteristics and key clinical inputs were sourced from a randomized phase 3 trial, whereas cost and utility values were derived from open-access databases and published literature. The primary outcomes assessed included quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Model uncertainty was addressed through probabilistic sensitivity, one-way sensitivity, and scenario analyses.</p> Results <p>In the base-case scenario, the addition of socazolimab to chemotherapy resulted in a marginal QALY gain of 0.09, at an incremental cost of $14,504.53, leading to an ICER of $152,228.60 per QALY. This ICER was below China’s willingness-to-pay (WTP) threshold of $40,354.27 per QALY, making it not cost-effective, with an INHB of −0.26 QALYs and an INMB of −$10,523.93. In the U.S., while the incremental QALY gain remained at 0.10, the additional cost increased to $85,599.55, yielding an ICER of $878,912.80 per QALY, far exceeding that of the U.S. WTP threshold of $150,000.00, confirming its lack of cost-effectiveness.</p> Conclusions <p>The combination of socazolimab with chemotherapy is not a cost-effective first-line treatment option for ES-SCLC in either China or the United States, highlighting the need for price adjustments and alternative treatment strategies to improve economic viability.</p>