SOX2 is a regulator of pluripotent cellular transcription, yet it has been recently integrated in cancer biology. The present study provides an analytic insight into the correlation of SOX2 overexpression with cancer metastasis and patient survival.To investigate the association of SOX2 overexpression with metastasis and its implication in the prognosis of cancer patients.A meta-analysis was conducted including studies that compared the association of low or high SOX2 expression with lymph node metastasis (LNM) and/or distant metastasis (DM). The following data were additionally extracted: survival, including the overall survival (OS) and disease-free survival (DFS), and prevalence of high and low SOX2 expression. Odds ratios (commonly known as ORs) and their respective 95% confidence intervals (CIs) were used to investigate the association between SOX2 expression and LNM and DM, while hazard ratios (commonly known as HRs) and 95%CIs were applied to evaluate the prognostic markers.In a total of 2643 patients (60.88% males), the pooled prevalence of SOX2 overexpression was 46.22% (95%CI: 39.07%-53.38%) in different types of cancer. SOX2 overexpression significantly correlated with DM (OR = 1.79, 95%CI: 1.20-3.25, < 0.008) compared to low SOX2 expression. In subgroups analyses, a high SOX2 expression was associated with LNM in cancers of the lung, breast, and colon and associated with DM in hepatic, head and neck, and colon cancers. SOX2 overexpression was also associated with a shorter OS (HR = 1.65, 95%CI: 1.34-2.04, < 0.001) and DFS (HR = 1.54, 95%CI: 1.14-2.08, = 0.005).A remarkable role of SOX2 overexpression was observed in cancer biology and metastasis. However, many questions in the regulatory pathways need to be addressed to reveal as many functional aspects as possible to tailor new targeted therapeutic strategies.