Background <p>Obesity is a rising global epidemic with profound effects on the health and well-being of both children and adults. Neighborhood racial and ethnic segregation, a key social determinant of health, has emerged as an important factor influencing obesity disparities across racial and ethnic groups. This study presents a systematic review to summarize and synthesize findings on the association between neighborhood racial and ethnic segregation and obesity, examining variations by race and ethnicity and identifying potential mediating and moderating mechanisms.</p> Methods <p>We searched five electronic databases, resulting in the inclusion of 19 quantitative studies in the final sample. Studies were screened for eligibility based on inclusion criteria, and data were extracted on study characteristics, outcomes, and identified mechanisms.</p> Results <p>Our findings showed a positive association between neighborhood racial and ethnic segregation and obesity among Black and Hispanic adults, particularly for Black women, suggesting that higher segregation is linked to increased obesity risk. However, the results were inconclusive for White, Asian, and American Indian adults. Limited studies on childhood obesity have restricted our ability to draw firm conclusions in this area. Neighborhood poverty emerged as a significant moderator, while neighborhood environments acted as a mediator, though evidence for these mechanisms remains sparse.</p> Discussion <p>This review highlights the significance of exploring moderating and mediating mechanisms, especially through longitudinal studies, to better understand how neighborhood racial and ethnic segregation affects obesity across various racial and ethnic groups. Fostering healthier environments may help reduce obesity disparities associated with neighborhood racial and ethnic segregation.</p>