OBJECTIVES:  This study sought to determine which of the drugs reimbursed by the Mexican Public Health System (MPHS) for the second-line (post platinum-containing chemotherapy) treatment of PD-L1 positive, advanced Non Small-Cell Lung Cancer (NSCLC, target population) is the most efficient, according to health technologies assessment literature. METHODS:  Through expert consultation, international/national guidelines of treatment review, and Mexican National Formulary assessment, it was determined that the relevant drugs for the analysis were Docetaxel, Pemetrexed and Gemcitabine. A systematic review of the literature was performed to identify relevant phase-III Randomized Controlled Trials (RCTs) and meta-analyses. Fourteen published articles were identified and a random-effects meta-analysis was performed using WINBUGS. A three-state Markov Model (Stable Disease, Progressing Disease and Death) was developed using a parametric fitting of Survival Curves, through a Constant Hazard-Ratio Model. The costs included were cost of the drug (CoD), administration/monitoring, grade 3/4 adverse events attention and Best Supportive Care (BSC) for progressed patients. Costs were obtained from published sources from Mexican government, except for BSC, which was obtained from a modified-Delphi expert panel. The time horizon was 2 years. A Public Payer's perspective was considered. Health outcome assessed was Life Years (LY). Discount rate was 5% for health and costs outcomes. A probabilistic sensitivity analysis (PSA) through Montecarlo simulations was performed. RESULTS:  The total cost of Treatment (CoT, in USD) for Docetaxel, Pemetrexed and Gemcitabine was $10,590, $16,500 and $9,850, respectively, where 21%, 37% and 4% was associated with the CoD. The number of LY for Docetaxel, Pemetrexed and Gemcitabine was 0.79, 0.87 and 0.91 respectively. These results were statistically-significant only for costs in the PSA. CONCLUSIONS:  Gemcitabine is a dominant, thus efficient strategy for the second-line treatment of PD-L1 positive advanced NSCLC from the MPHS perspective. Even under uncertainty, gemcitabine is a cost-saving alternative compared to Docetaxel and Pemetrexed.