•Currently, nasopharyngeal carcinoma(NPC) stands as a significant cancer posing a threat to human health, with approximately three-quarters of cases being diagnosed at the locally advanced stage.•While multiple treatment options exist for locally advanced NPC, the determination of the most clinically beneficial and cost-effective approach remains unclear.•The objective of this study is to construct Network Meta-Analysis (NMA) and Cost-Effectiveness Analysis (CEA) models to assess which treatment strategy yields the maximum benefit.•Our research team specializes in clinical diagnosis, treatment, and efficacy prediction for NPC, with notable achievements in pharmacoeconomics.•Through this study, we aim to provide a therapeutic guidance for clinical practitioners by evaluating the comparative benefits of different treatment modalities. The ultimate goal is to contribute valuable insights for healthcare professionals in the field. The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.