Indocyanine Green (ICG) is a promising technique for the assessment of gastric conduit and anastomosis perfusion during esophagectomy. ICG integration may be helpful in minimizing the risk of anastomotic leak (AL). Literature evidence is sparse, while the real effect of ICG assessment on AL minimization remains unsolved. The aim of this systematic review and meta-analysis was to compare short-term outcomes between ICG-guided and non-ICG-guided (nICG) esophagogastric anastomosis during esophagectomy for cancer. Materials and Methods: PubMed, MEDLINE, Scopus,Web of Science, Cochrane Central Library, and ClinicalTrials.gov were queried up to 25 April 2024. Studies that reported short-term outcomes for ICG versus non-ICG-guided (nICG) anastomosis in patients undergoing esophagectomy were considered. Primary outcome was AL. Risk ratio (RR) and standardized mean difference (SMD) were utilized as effect size measures, whereas to assess relative inference we used 95% confidence intervals (95% CI). Results: Overall, 1399 patients (11 observational studies) were included. Overall, 576 (41.2%) underwent ICG gastric conduit assessment. The patients’ ages ranged from 22 to 91 years, with 73% being male. The cumulative incidence of AL was 10.4% for ICG and 15.4% for nICG. Compared to nICG, ICG utilization was related to a reduced risk for postoperative AL (RR 0.48; 95% CI 0.23–0.99; p = 0.05). No differences were found in terms of pulmonary complications (RR 0.83), operative time (SMD −0.47), hospital length of stay (SMD −0.16), or 90-day mortality (RR 1.70). Conclusions: Our study seems to indicate a potential impact of ICG in reducing post-esophagectomy AL. However, because of limitations in the design of the included studies, allocation/reporting bias, variable definitions of AL, and heterogeneity in ICG use, caution is required to avoid potential overestimation of the ICG effect.