It is estimated that 390 million dengue infections occur every year worldwide. The dengue virus can produce a spectrum of clinical manifestations ranging from asymptomatic infection to serious illness, such as Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), which can lead to death. In Latin America, severe dengue is one of the leading causes of serious illness and death, especially among children. The study aims to systematically review the literature to identify, by meta-analysis, risk factors related to severe dengue in Latin America. This systematic review was conducted following the recommendations of the PRISMA and PICOS strategies. PubMed, SciELO, LILACS, and EMBASE databases were used to search for scientific articles eligible for the study. Keywords were selected using the MeSH tool combined with Boolean connectors. Inclusion and exclusion criteria were applied for the studies selection, and the association measures such as Odds ratio (OR), Relative risk (RR), Hazard ratio (HR), or Prevalence ratio (PR) were collected for the meta-analysis. Data were analyzed using STATA v 16.0 software. In total, 43 articles were included in the systematic review, twenty-four were from studies in Brazil, followed by seven studies in Paraguay and four in Colombia. The percentage of severe cases in the studies ranged from 1% to 71%, and two studies included only severe patients. Fifteen articles brought the data on death due to dengue, the percentage ranging from 0.04% to 24%, and one study analyzed only deaths as a severe outcome. The most common risk factors for DSS, DHF, or severe dengue with a statistically significant association were abdominal pain, hepatomegaly, nausea or vomiting, and the presence of petechiae. The baseline diseases such as anemia, diabetes, allergy, asthma, and cardiovascular problems were not very frequent, but when combined in the category of comorbidities, it shows a relevant frequency. The most frequent and statistically significant risk factors related to death from the disease were the presence of warning signs and the development of plasma leakage, DSS or DHF, followed by nausea and vomiting and low platelet count. Analyzes of the meta-analysis results are still ongoing and will help to better identify risk factors. Thus, cases of severe dengue can be frequent in Latin American countries, and it is important to implement control and prevention measures, especially in those with certain signs, symptoms, and comorbidities. In addition, to avoid the risk of death from the disease, better care is needed for those who develop warning signs, DSS, or DHF. Financial Support: Not applicable.