Residential location is thought to influence people's well-being, but different individuals may value residential areas differently. We examined how life satisfaction and personality traits are geographically distributed within the UK London metropolitan area, and how the strength of associations between personality traits and life satisfaction vary by residential location (i.e., personality-neighborhood interactions). Residential area was recorded at the level of postal districts (216 districts, n = 56,019 participants). Results indicated that the strength of associations between personality traits and life satisfaction depended on neighborhood characteristics. Higher openness to experience was more positively associated with life satisfaction in postal districts characterized by higher average openness to experience, population density, and ethnic diversity. Higher agreeableness and conscientiousness were more strongly associated with life satisfaction in postal districts with lower overall levels of life satisfaction. The associations of extraversion and emotional stability were not modified by neighborhood characteristics. These findings suggest that people's life satisfaction depends, in part, on the interaction between individual personality and particular features of the places they live.