The shift in dietary habits has reshaped the population’s health profile, leading to a rise in overweight individuals and a subsequent decline in health-related quality of life (HRQoL). This study evaluated the correlations between demographic, social, and health-related factors and HRQoL in rural and urban areas of Bahia, Brazil. The cross-sectional study included 124 participants aged 18–60 who underwent interviews, anthropometric measurements, and laboratory tests. The WHOQol-BREF instrument assessed the HRQoL. The results showed that rural participants had lower educational levels, income, and access to sanitation. Despite these challenges, rural residents reported better HRQoL in psychological, social relations, and health satisfaction domains, although differences diminished after age adjustment. Urban participants, who had higher rates of obesity and related metabolic risks experienced a negative correlation between BMI and HRQoL, especially in the social relationships domain. The study highlights that environmental and social factors, such as weight-related stigma and social connections, significantly influence HRQoL in urban areas, emphasizing the need for public health interventions that address both nutritional status and urban-specific challenges.