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Objective This descriptive cross-sectional study aimed to determine how cognitive, disease, and environmental variables relate to social–emotional functioning in youth with NF1 and plexiform neurofibromas. Methods Psychological assessments were administered to 53 children (mean age 12.4 years); parents and teachers completed the Behavior Assessment System for Children—Second Edition (BASC-2). Disease severity was quantified by nurse–practitioner ratings and tumor burden, and parents completed a life events checklist to indicate environmental stressors. Results Notable proportions of children scored in the at-risk/clinically significant ranges on several parent and teacher BASC-2 subscales including Somatization, Attention Problems, Depression, and Withdrawal. Combinations of cognitive, disease, and environmental variables predicted scores on parent BASC-2 Internalizing Problems, Behavior Symptoms Index, and Adaptive Skills composites. Conclusions Cognitive, disease, and environmental variables relate to social–emotional outcomes in children with NF1. These youth may benefit from interventions targeting social skills, cognitive functioning, and adaptive ways of coping with NF1-related pain.