Since early May 2022, an increasing number of Monkeypox (Mpox) cases have been reported in non-endemic regions of the world. The Mpox outbreak has undergone significant changes in epidemiologic characteristics and clinical manifestations compared to the past. Therefore, a systematic review and meta-analysis of the information collected during this outbreak is particularly important in order to improve the understanding of the disease and to provide a reference basis for the clinical management of Mpox-infected patients.Relevant studies published from May 7, 2022 to December 31, 2023 were searched. Overall, 49 articles were finally identified and analyzed. Mpox outbreak spreads globally, all ages at risk, young people at higher risk. Transmission was predominantly sexual 88.2% (95% confidence interval [CI] 79.4-94.8%), with homosexual transmission 85.5% (95%CI 74.4-93.8%) being the most common, and heterosexual 35.7% (95%CI 8.2-69.9%) and bisexual 4.4% (95%CI 0.0-15.2%) transmission also occurring. Skin lesions 88.8% (95%CI 81.8-94.3%), fever 57.4% (95%CI 50.5-64.3%) and lymphadenopathy 55.5% (95%CI 47.5-62.3%) were the most frequent clinical signs. Ocular lesions 15.2% (95%CI 4.3-31.9%) and oral lesions 21.3% (95% CI 10.5-35.7%) were also frequent. Skin lesions were most common on the genitals 52.5% (95%CI 44.5-59.4%) and lymphadenopathy was most frequent in the groin 39.5% (95% CI 31.9-48.5%).