ObjectiveTo explore the best neoadjuvant treatment strategy for esophageal cancer and provide a theoretical basis for clinical formulation of neoadjuvant treatment plan. MethodsPubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang, and VIP were searched from inception to May 2022. Two researchers independently performed literature screening and data extraction. The quality of the studies was evaluated by the Cochrane risk of bias tool, and data analysis was performed in RStudio environment using R3.6.3 software. ResultsA total of 24 studies were included, covering 5 286 patients treated with surgery alone, neoadjuvant chemotherapy (NCT), neoadjuvant radiotherapy (NRT), or neoadjuvant chemoradiotherapy (NCRT) followed by combined surgical treatment. The risk of bias of the studies was low. The results of the network meta-analysis showed that combined surgical treatments after NCRT [HR=0.77, 95%CI (0.70, 0.85)] and NCT [HR=0.89, 95%CI (0.81, 0.98)] were effective methods to improve patients' overall survival (OS) compared with surgery alone. In addition, NCRT could significantly reduce the incidence of local recurrence [OR=0.43, 95%CI (0.30, 0.58)] and distant metastasis [OR=0.71, 95%CI (0.52, 0.93)] in patients with esophageal cancer. However, NCRT [RR=1.30, 95%CI (0.77, 2.20)] increased the mortality rate of patients at 30 d after surgery. ConclusionThe available evidence suggests that NCRT combined with surgery is the best option for treating patients with resectable esophageal cancer, but this treatment carries the risk of increased 30 d postoperative mortality. Future studies should focus on optimizing the NCRT regimen with the aim of improving patients’ OS while effectively reducing postoperative mortality. In addition, more high-quality randomized controlled trials are needed to support the results of the study.