Background: Overweight and obesity remain major public health challenges in Puerto Rico, affecting over 70% of adults and contributing to cardiovascular, metabolic, and mental health disorders. This study explores the psychosocial and behavioral factors influencing obesity within low-income Puerto Rican communities, emphasizing both biological sex differences and socially defined sex-role influences, along with their respective mental health dimensions. Method: Using a qualitative approach, Community-Based Participatory Research (CBPR), ten focus groups were conducted with 71 participants (37 women and 34 men) from two municipalities in southern Puerto Rico. Discussions were analyzed thematically with the Socioecological and Health Belief Models to identify key determinants. Results: The data collected revealed that women expressed greater emotional vulnerability, frequently citing anxiety, depression, body image concerns, and stress-related eating as contributors to obesity. Men, meanwhile, reported frustration with diet adherence, economic limitations, and healthcare inaccessibility. Across participants, economic hardship, cultural norms, and limited health education emerged as major obstacles. Conclusions: Findings underscore the need for holistic, sex-informed and socially responsive interventions that integrate mental health support with nutritional and physical health strategies. Addressing self-esteem, emotional regulation, and stress management alongside behavioral modification can promote sustainable, culturally tailored obesity prevention in Puerto Rico.