Background: Recent studies have demonstrated that preoperative neoadjuvant therapy in esophageal carcinoma can bring extra survival benefits compared to surgical resection alone or postoperative adjuvant therapy. There is still a lack of high-level evidence from large randomized controlled clinical trials to define the interval between neoadjuvant therapy and surgery, radiotherapy dose and target area plans after neoadjuvant treatment, therefore we adopted a meta-analysis to compare the efficacy and safety of different neoadjuvant treatment options in esophageal squamous cell carcinoma (ESCC) in these clinical studies. Methods: Articles were retrieved from PubMed, Cochrane, Embase, Web of Science databases and abstracts of ASCO and ESMO meetings in 2021-2022 by the terms esophageal cancer, neoadjuvant therapy, Inclusion criteria: a: Patients with excisable stage esophageal cancer. Histopathological confirmed squamous carcinoma of the esophagus; b: At least one reported primary outcome as follows: pathological complete response (pCR) rate; major pathological response (MPR) rate. Statistical analysis was performed on Stata 16.0 and R 4.0 with a significance level of 0.05. Results: A total of 39 clinical studies with a total of 2,434 patients, mostly male, were included, with a predominance of phase 2 trials. 16 neoadjuvant chemotherapy combined with immunotherapy (nICT), 2 neoadjuvant immunotherapy alone, 5 neoadjuvant chemoradiotherapy combined with immunotherapy (nICRT), 15 neoadjuvant chemoradiotherapy (nCRT), 1 neoadjuvant chemotherapy, 32 single-arm studies, and 7 randomized controlled trials. The overall neoadjuvant therapy pCR rate was 36% (95% CI: 32%-40%) and the overall MPR rate was 55% (95% CI: 47%-63%). The nICT pathological complete response rate was 31% (95% CI: 26%-36%), nCRT pathological complete response rate was 38% (95% CI: 32%-44%) and nICRT complete pathological response rate was 49% (95% CI: 39% -59%). Complete pathological response rates were 36% (95% CI: 31%-41%) for neoadjuvant immunotherapy (with immunotherapy) and 33% (95% CI: 13%-54%) for neoadjuvant immunotherapy alone. 26 studies had a mean R0 resection rate of 93%, with the majority of patients achieving R0 resection. Conclusions: From this Meta-analysis it can be concluded that nICRT has the best complete pathological response rate of all neoadjuvant treatments and nCRT has a better complete pathological reponse rate than nICT, but most of them are not phase 3 clinical trials, therefore more studies are needed to further clarify the benefit of neoadjuvant radiotherapy combined with immunotherapy in esophageal squamous cell carcinoma.