ImportanceNeighborhood-level disadvantage is an important factor in the creation and persistence of underresourced neighborhoods with an undue burden of disparate breast cancer–specific survival outcomes. Although studies have evaluated neighborhood-level disadvantage and breast cancer–specific survival after accounting for individual-level socioeconomic status (SES) in large national cancer databases, these studies are limited by age, socioeconomic, and racial and ethnic diversity.ObjectiveTo investigate neighborhood SES (using a validated comprehensive composite measure) and breast cancer–specific survival in a majority-minority population.Design, Setting, and ParticipantsThis retrospective multi-institutional cohort study included patients with stage I to IV breast cancer treated at a National Cancer Institute–designated cancer center and sister safety-net hospital from January 10, 2007, to September 9, 2016. Mean (SD) follow-up time was 60.3 (41.4) months. Data analysis was performed from March 2022 to March 2023.ExposuresNeighborhood SES was measured using the Area Deprivation Index (tertiles), a validated comprehensive composite measure of neighborhood SES.Main Outcomes and MeasuresThe primary outcome was breast cancer–specific survival. Random effects frailty models for breast cancer–specific survival were performed controlling for individual-level sociodemographic, comorbidity, breast cancer risk factor, access to care, tumor, and National Comprehensive Cancer Network guideline-concordant treatment characteristics. The Area Deprivation Index was calculated for each patient at the census block group level and categorized into tertiles (T1-T3).ResultsA total of 5027 women with breast cancer were included: 55.8% were Hispanic, 17.5% were non-Hispanic Black, and 27.0% were non-Hispanic White. Mean (SD) age was 55.5 (11.7) years. Women living in the most disadvantaged neighborhoods (T3) had shorter breast cancer–specific survival compared with those living in the most advantaged neighborhoods (T1) after controlling for individual-level sociodemographic, comorbidity, breast cancer risk factor, access to care, tumor, and National Comprehensive Cancer Network guideline-concordant treatment characteristics (T3 vs T1: hazard ratio, 1.29; 95% CI, 1.01-1.65; P < .04).Conclusions and RelevanceIn this cohort study, a shorter breast cancer–specific survival in women from disadvantaged neighborhoods compared with advantaged neighborhoods was identified, even after controlling for individual-level sociodemographic, comorbidity, breast cancer risk factor, access to care, tumor, and National Comprehensive Cancer Network guideline-concordant treatment characteristics. The findings suggest potential unaccounted mechanisms, including unmeasured social determinants of health and access to care measures. This study also lays the foundation for future research to evaluate whether social adversity from living in a disadvantaged neighborhood is associated with more aggressive tumor biologic factors, and ultimately shorter breast cancer-specific survival, through social genomic and/or epigenomic alterations.