Background: The ideal surgical approach for empyema in children (≤18 years) remains controversial. Video assisted thoracoscopic surgery (VATS) and chest drain with fibrinolysis (CDF) are both accepted methods. The aim of this study was to clarify which of these two techniques provides the best clinical outcome. Methods: A systematic review and meta-analysis (1997–2018) was conducted. We used the random-effect model to produce risk ratio (RR) for categorical variables, and standard difference in means (SDM) for continuous variables, along with 95% confidence intervals [CI]. I 2 value was used to assess heterogeneity. P values <0.05 were considered significant. Results: We identified 707 studies: 10 studies were included in the final analysis. The incidence of total peri-operative complications was not different between the two groups (RR 0.6 [CI: 0.3–1.2], p = 0.2; I 2 = 0.0%; p = 0.6). Need for re-intervention was significantly lower in the VATS group (RR 0.55 [CI: 0.34–0.88], p = 0.01; I 2 = 14.4%; p = 0.3). Post-operative length of hospital stay was significantly shorter in the VATS group (SDM −0.45 [CI: −0.78 to −0.12], p = 0.007; I 2 = 88%; p = 0.001). Conclusions: Current evidence suggests that VATS and CDF for empyema in children have a similar incidence of peri-operative complications. However, VATS seems associated with reduced need for re-intervention and shorter post-operative hospital stay.