This systematic review and meta-analysis aims to synthesize evidence on the epidemiology, prevention, and treatment of monkeypox (mpox) in children and pregnant individuals, particularly in endemic countries. The study searched multiple databases from inception to April 17, 2023, and included studies reporting primary data on confirmed, suspected, or probable cases of mpox in humans or the use of vaccines and therapeutics. The review included 61 studies, with 53 reporting pediatric outcomes (n=2123 cases), seven reporting maternal or congenital outcomes (n=32 cases), two reporting vaccine safety (n=28 recipients), and three reporting transmission during breastfeeding (n=4 cases). The most common clinical features in children were rash (100%), fever (73%), and lymphadenopathy (47%). Among pregnant individuals, rash was reported in 100% of cases, while fever and lymphadenopathy were less common. Most pediatric complications arose from secondary bacterial infections. The pooled pediatric case fatality ratio was 11% (95% CI 4–20). In pregnancies, half resulted in fetal death. The study highlights critical knowledge gaps and recommends increased funding, international collaboration, and equitable research to inform control strategies for at-risk communities in endemic countries.This systematic review and meta-analysis aims to synthesize evidence on the epidemiology, prevention, and treatment of monkeypox (mpox) in children and pregnant individuals, particularly in endemic countries. The study searched multiple databases from inception to April 17, 2023, and included studies reporting primary data on confirmed, suspected, or probable cases of mpox in humans or the use of vaccines and therapeutics. The review included 61 studies, with 53 reporting pediatric outcomes (n=2123 cases), seven reporting maternal or congenital outcomes (n=32 cases), two reporting vaccine safety (n=28 recipients), and three reporting transmission during breastfeeding (n=4 cases). The most common clinical features in children were rash (100%), fever (73%), and lymphadenopathy (47%). Among pregnant individuals, rash was reported in 100% of cases, while fever and lymphadenopathy were less common. Most pediatric complications arose from secondary bacterial infections. The pooled pediatric case fatality ratio was 11% (95% CI 4–20). In pregnancies, half resulted in fetal death. The study highlights critical knowledge gaps and recommends increased funding, international collaboration, and equitable research to inform control strategies for at-risk communities in endemic countries.