Objective <p>Neighborhood stressors may impact mental health; yet, little research has assessed whether associations differ by perceived stress among young adults. This study assessed US young adults’ experiences of neighborhood stressors in relation to mental health symptoms and the moderating role of perceived stress.</p> Methods <p>We surveyed 3,191 US young adults ages 18–34 (M_age=26.4 years; 60.9% female; 16.8% sexual minority; 12.0% Black, 14.6% Asian, 6.6% Other race; 18.7% Hispanic) in February-May 2025. Measures included neighborhood stressors: structural disadvantage, health/services access disadvantage, and discrimination; perceived stress (PSS-4); and mental health symptoms (PHQ-4). Multivariable linear regression assessed neighborhood stressors, perceived stress, and their interaction in relation to PHQ-4 scores, controlling for sociodemographics.</p> Results <p>All 3 neighborhood stress factors and perceived stress were independently associated with higher PHQ-4 (p’s&lt;0.001). Multivariable results showed that factors associated with higher PHQ-4 included health/service access disadvantage and perceived stress. Moreover, the effect of structural disadvantage on PHQ-4 were stronger with higher stress levels. Additionally, being sexual minority (vs. heterosexual), White (vs. Black), and single/other relationship status (vs. married) were associated with higher PHQ-4.</p> Conclusions <p>Neighborhood disparities and their associations with mental health symptoms highlight the importance of neighborhood-level prevention strategies and public health efforts to reduce inequities.</p>