Neighborhood adversity links to mental health and cognitive outcomes, but little is known about structural factors that may buffer these links. The current study addresses this gap by assessing the role of protective factors in the association of neighborhood deprivation, threat, and segregation with psychopathology symptoms and cognitive outcomes. Linear mixed models were run in ABCD sample participants (n = 5812) to test associations of neighborhood Area Deprivation Index (ADI; deprivation), crime (threat), and dissimilarity and interaction index (segregation) with attention difficulties, internalizing and externalizing symptoms, psychotic-like experiences (PLEs), and fluid and crystallized cognitive performance. School environment, neighborhood education child opportunity index, neighborhood cohesion, and green space were tested as moderators of the association of neighborhood adversity with outcomes. Higher neighborhood educational resources buffered the association of neighborhood deprivation with crystallized cognitive performance. The association of higher neighborhood crime with externalizing symptoms was weaker for youth in less supportive school environments. Further, higher neighborhood segregation was associated with internalizing symptoms more strongly for youth with more neighborhood educational resources. Taken together, results suggest adverse neighborhood environments are associated with higher psychopathology symptoms and lower cognitive performance. Access of neighborhood educational resources could buffer links of neighborhood deprivation and cognitive performance. While evidence of protective links was not widespread, studying these patterns is necessary for understanding possible environmental contributors to mental health and cognitive function. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=dpGkdPkPiSw.