Background Multisystem inflammatory syndrome in children (MIS‐C) associated with coronavirus disease 2019 has been increasingly recognized. However, the clinical features of MIS‐C and the differences from Kawasaki disease remain unknown. The study aims to investigate the epidemiology and clinical course of MIS‐C. Methods PubMed and EMBASE were searched through August 30, 2020. Observational studies describing MIS‐C were included. Data regarding demographic features, clinical symptoms, laboratory, echocardiography and radiology findings, treatments, and outcomes were extracted. Study‐specific estimates were combined using one‐group meta‐analysis in a random‐effects model. Results A total of 27 studies were identified including 917 MIS‐C patients. The mean age was 9.3 (95% confidence interval CI, 8.4–10.1). The pooled proportions of Hispanic and Black cases were 34.6% (95% CI, 28.3–40.9) and 31.5% (95% CI, 24.8–38.1), respectively. The common manifestations were gastrointestinal symptoms (87.3%; 95% CI, 82.9–91.6) and cardiovascular involvement such as myocardial dysfunction (55.3%; 95% CI, 42.4–68.2), coronary artery aneurysms (21.7%; 95% CI, 12.8–30.1) and shock (65.8%; 95% CI, 51.1–80.4), with marked elevated inflammatory and cardiac markers. The majority of patients received intravenous immunoglobulin (81.0%; 95% CI, 75.0–86.9), aspirin (67.3%; 95% CI, 48.8–85.7), and corticosteroids (63.6%; 95% CI, 53.4–73.8) with a variety of anti‐inflammatory agents. Although myocardial dysfunction improved in 55.1% (95% CI, 33.4–76.8) at discharge, the rate of extracorporeal membrane oxygenation use was 6.3% (95% CI, 2.8–9.8) and the mortality was 1.9% (95% CI, 1.0–2.8). Conclusion Our findings suggest that MIS‐C leads to multiple organ failure, including gastrointestinal manifestations, myocardial dysfunction and coronary abnormalities, and has distinct features from Kawasaki disease.