In low- and middle-income countries (LMICs), children and families face a multitude of risk factors for mental health and well-being. These risks are even further exacerbated in humanitarian emergencies. However, access to effective mental health services in such settings is severely limited, leading to a large mental health treatment gap. Middle childhood (5–12 years) is a crucial period for human development during which symptoms of emotional distress often emerge, with one in three mental disorders developing prior to age 14. However, there is little evidence of effective psychological interventions for children in this developmental stage, and suitable for implementation within LMICs and humanitarian emergencies. We conducted this evidence review to inform the development of a new intervention package based on existing best practice for this age group, drawing insights from both global and LMIC resources. Our review synthesizes the findings of 52 intervention studies from LMICs and humanitarian settings; 53 existing systematic reviews and meta-analyses covering both LMICs and high-income countries, and 15 technical guidelines. Overall, there is limited high-quality evidence from which to draw recommendations for this age group; however, some promising intervention approaches were identified for children experiencing externalizing and internalizing symptoms, traumatic stress and a combination of difficulties. Several effective interventions utilize cognitive-behavioral techniques for children, in either group or individual format, and incorporate caregiver skills training into treatment, although the findings are mixed. Most evaluated interventions use specialists as delivery agents and are lengthy, which poses challenges for scale-up in settings where financial and human resources are scarce. These findings will inform the development of new psychological interventions for children in this age group with emotional and behavioral difficulties.