Background <p>Home environments improve quality of life and reduce infections for children on long-term mechanical ventilation via tracheostomy (LTMV-T). However, unexpected hospital readmissions and death remain significant concerns. Existing systematic reviews have not fully examined risk factors for readmission and mortality. This review examines modifiable and non-modifiable risk factors associated with readmission and mortality in infants, children, and adolescents on LTMV-T.</p> Methods <p>Five databases (PubMed, CINAHL, Web of Science, Embase, and Epistemonikos) were searched from inception to 2024. All quantitative study designs examining risk factors associated with readmission and/or mortality in children less than 21&#xa0;years of age on LTMV-T were included. Articles were limited to peer-reviewed journals and the English language. Covidence software was used for data management, study screening, and data extraction. Each abstract was reviewed by two independent reviewers and discrepancies were resolved by a third. The Joanna Briggs Institute critical appraisal tools were used to assess risk of bias in individual studies.</p> Results <p>Twenty-six studies examined cohorts of children on LTMV-T from 1980 to 2023. Studies were primarily retrospective cohorts, with sample sizes ranging from 27 to 8,009 children. Most studies reported that at least 50% of readmissions occurred within the first two years post-discharge and respiratory-related issues accounted for 30–75% of readmissions. Mortality within the first-year post-discharge varied as low as 0% to as high as 16%. Few studies examined socioenvironmental risk factors or those specific to LTMV-T populations, conducting analyses primarily on tracheostomy-only and/or LTMV-T cohorts. Risk factors for readmission and mortality included age, lower income, discharge disposition, chronic conditions, lack of respiratory physiotherapy (cough assist, percussions), gastrostomy tube, and lower birth weight. Risk of bias ranged from low to moderate due to unclear outcome measures and analyses that did not address potential confounders.</p> Conclusions <p>Readmissions are common occurrences among children on LTMV-T with considerable risk of mortality, especially within the first two-years post-discharge. Risk factors identified were predominately clinical and demographic characteristics that can inform risk assessments and targeted interventions. Future studies should further explore socioenvironmental factors such as social determinants of health among LTMV-T specific populations.</p> Trial registration <p>International Prospective Register of Systematic Reviews ID: CRD42024492773.</p>