INTRODUCTION: Benmelstobart and anlotinib plus etoposide-carboplatin (EC) group has demonstrated substantial clinical efficacy in improving survival outcomes for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, the high treatment cost raises concerns regarding its affordability and cost-effectiveness across healthcare systems with heterogeneous pricing and reimbursement mechanisms. AIM: This study aimed to evaluate the cost-effectiveness of benmelstobart and anlotinib plus EC group compared to EC alone group and anlotinib plus EC group from both US and Chinese payer perspectives. The findings are intended to inform value-based pricing strategies and evidence-based reimbursement decision-making. METHOD: A partitioned survival model (PSM) with a lifetime horizon and 21-day cycles was constructed using clinical data from the ETER701 trial. Direct medical costs and health utility inputs were obtained from national databases, local hospitals, and published literature. The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated by comparing costs and quality-adjusted life years (QALYs) between treatment strategies. Scenario analyses, including drug price simulations and deterministic and probabilistic sensitivity analyses, were conducted to evaluate model robustness. Willingness-to-pay (WTP) thresholds were set at $100,000/QALY and $150,000/QALY (US) and $40,011/QALY (China). RESULTS: In the US, the benmelstobart and anlotinib plus EC group yielded ICER of $121,560.40/QALY versus EC alone group and $127,579.09/QALY versus anlotinib plus EC group, both below the $150,000/QALY threshold. However, at the $100,000/QALY threshold, cost-effectiveness would require reducing benmelstobart's price to $1316.12/600 mg. In China, the ICER of $117,667.17/QALY exceeded the local threshold. Price simulations suggested that cost-effectiveness could be achieved if prices were reduced below $2230.60/600 mg (US) and $328.47/600 mg (China). Sensitivity analyses identified progression-free survival (PFS) utility and benmelstobart pricing as major cost drivers. Probabilistic analysis indicated a 75.1% probability of cost-effectiveness at $150,000/QALY in the US. However, the probability of cost-effectiveness is 0% at WTP thresholds of $100,000/QALY in the US and $40,011/QALY in China. CONCLUSION: Benmelstobart plus anlotinib and EC group is likely to be cost-effective in the US at a WTP threshold of $150,000/QALY, but not in China at current prices. An 80% price reduction in China would be necessary to align with its WTP threshold, emphasizing the need for policy interventions in drug pricing and reimbursement to improve patient access.