Background Hispanic/Latino (H/L) cancer survivors in medically underrepresented areas like South Texas (STX) face disproportionate burdens in post-treatment outcomes. Familismo—a core cultural value emphasizing family loyalty, interconnectedness, and prioritizing family needs—may influence recovery, health behaviors, and research participation. However, its relationship with outcomes such as treatment adherence, recurrence, and health-related quality of life (HRQoL), as well as proximity to the US–Mexico border, remains poorly understood. This study aims to assess whether familismo influences treatment adherence, cancer recurrence, and HRQoL (physical, emotional, social, and functional well-being) among H/L cancer survivors in STX. In addition, it examines familismo’s potential associations with proximity to the US Mexico border, and explores familial obligation as potential barriers to research participation. Methods A cross-sectional analysis was performed using baseline data from Avanzando Caminos, an ongoing NCI-funded prospective cohort study exploring the biopsychosocial, cultural, and environmental determinants of health outcomes in H/L cancer survivors. Participants (n = 365) had completed primary treatment for breast, colorectal, stomach, lung, prostate, cervical, liver, or kidney cancers within the past 10 years. Familismo was measured using Sabogal’s validated 15-item scale, HRQoL with the Functional Assessment of Cancer Therapy–General (FACT-G), and treatment adherence, cancer recurrence, and zip code were self-reported. Regression models adjusted for age, sex, marital status, and cancer type. Shortest distances between centroid latitudes and longitudes of each respective zip code were mapped to a model of the US–Mexico border created with Python. Results Familismo was a significant positive predictor of HRQoL (β=0.107, p=0.041), but not significantly associated with treatment adherence or cancer recurrence. No significant association was found between distance to the US–Mexico border and familismo levels. Qualitative review of the pre-screening data revealed that 13% of eligible patients who declined study participation cited family-related barriers, such as caregiver burden and familial decisionmaking, supporting the relevance of familismo as a factor in research engagement. Conclusion Findings suggest that familismo may support emotional resilience, and underscore the importance of incorporating cultural values like familismo into survivorship care to improve quality of life and reduce health inconsistencies among H/L cancer survivors. Future studies should explore targeted family-based interventions to optimize survivorship care and strategies to reduce familial barriers to research engagement among H/L cancer survivors.