Background: Prolonged parental separation at young ages has significant adverse effects on development in left-behind-children (LBC). We aimed to compare mental health status, emotional and behavioural problems, and their association with socioemotional development between LBC and their counterparts. Methods: Cross-sectional studies comparing LBC and non-LBC published from 2000 onwards were searched. Primary outcomes included depression, anxiety emotional and behavioural problems. Secondary outcomes included loneliness, self-harm, suicide, and risk-related behaviours. Quality of all included articles was assessed by Joanna Briggs Institute (JBI) critical appraisal. Data was analyzed by random model-based effect method. Results: 78 observational studies comprising of 394,308 children aged 2–18 were included. Compared to NLBC, LBC had significantly more depression, anxiety, emotional and behavioural problems, conduct problems, self-harm, loneliness, peer bullying, attempts of smoking and alcohol consumption. Subgroup analyses found that younger LBC between the ages of 6 to 12 were at greater risks of poor mental health, emotional and behavioural problems. Conclusion: Absent parental care prevents healthy socio-emotional development and hinder the formation of secure attachment. Poor social-emotional development leads to worse emotional resilience against psychological stressors, while LBC residing in rural areas also experience additional risk factors of low household income and poor access to mental health services. Impact statement: Prolonged parental separation negatively influences mental health, especially in younger children between the ages 6 to 12. Poor social-emotional development in left-behind children is associated with worse emotional resilience against psychological stressors. Additional risk factors including residing in rural areas, low household income, and poor access to mental health services predisposes left-behind children to high risks of mental illness. Timely support services targeted towards strengthening resilience factor such as learning better emotional and behavioural coping strategies and improving school and peer support to address increased risk of mental health problems are required for current left-behind children.