The Neurodevelopmental Ecological Screening Tool (NEST) is a new instrument to screen children for developmental challenges. This article describes the validation of the NEST neurodevelopmental domain. Data were collected from a nationwide purposely restricted sample of caregivers of children aged 3-5 years (n = 231) living in poverty and experiencing homelessness. We used Rasch-based Rating Scale Models to select items with good fit. Cronbach's alpha was used to measure the internal consistency validity of the entire neurodevelopmental domain. Construct validity and dimensional structure were obtained using confirmatory factor analysis. Interclass correlations were used to measure the test-retest reliability of the subdomains. Neurodevelopmental Ecological Screening Tool scores were compared to results on clinician-administered gold standard measures for a subsample (n = 48). The neurodevelopmental domain score represents a single overarching risk construct with some variance attributable to distinct developmental constructs and validly and reliably identifies a child's level of developmental risk.