Background <p>In principle, reimbursement decisions for oncological drugs in Spain hinge on clinical benefit and cost-effectiveness, yet factors guiding these decisions are not fully explained in reimbursement reports. This study examines these criteria for a cohort of lung cancer drugs in Spain and estimates and describes the cost-effectiveness, clinical benefit, and reimbursement decisions for lung cancer and mesothelioma drugs authorized in Spain between 2010 and 2023.</p> Materials and methods <p>Clinical benefit was assessed using four scales from medical societies and Health Technology Assessment Agencies (HTAA). Cost-effectiveness was estimated using notified and reimbursed prices, and effects were obtained from HTAA reports. Reimbursement decisions were reviewed from official sources (BIFIMED). Statistical analyses and models were carried out to determine influencing factors.</p> Results <p>28 drugs and 55 indications were analysed. A total of 50 drugs and 165 indications were excluded from the analysis as they were not related to lung cancer. A positive association was found between clinical benefit and reimbursement decision (OR: 3.20; CI95%: 1.46–7.44; <i>p</i> &lt; 0.01). The median of the estimated incremental cost-utility ratio (ICUR) was €91,568 (IQR 43,944 − 133,384) per Quality-Adjusted Life Year (QALY) gained with notified prices and €41,030/QALY (IQR 22,213 − 76,390) with reimbursed prices (<i>p</i> &lt; 0.0001). Statistical models showed that substantial clinical benefit increased the probability of positive reimbursement decision by 35–40% points. Cost-effectiveness, presence of therapeutic alternatives, disease incidence or presence of uncertainty had no significant influence.</p> Conclusions <p>Our study reveals a positive association between clinical benefit and reimbursement decisions for lung cancer drugs in Spain. No evidence was found that cost-effectiveness is associated with reimbursement decisions.</p>