This study was conducted to identify the challenges faced by medical rescue teams during the response phase of sudden-onset disasters and provide a comprehensive understanding of these challenges. Peer-reviewed, English-language articles published until January 2023 that described the challenges faced by medical rescue teams during disaster response were searched in the Web of Science, Scopus, Cochrane, PubMed, and Science Direct databases. The articles were assessed using the Mixed Methods Appraisal Tool (MMAT) version 2018, a quality evaluation tool, and a qualitative thematic synthesis approach was adopted. A total of 353 publications were identified, and 18 of these met the inclusion criteria. Of the 18 included studies, 8 were review articles, 4 were special reports, 3 were cross-sectional studies, 1 was a mixed methods study, 1 was a qualitative study, and 1 was a short communication. Through qualitative analysis, the challenges faced by medical rescue teams during disaster response were categorized into 6 factors: organizational, individual, environmental and health, logistical, communication and information, and other factors. These factors are significant in terms of issues such as delayed access to disaster victims, disruptions in response processes, and an increase in morbidity and mortality rates. Therefore, the findings in our study shed light on future research in the field of disasters and offer opportunities to develop a roadmap for improving the conditions of medical rescue teams.