Objective: Chagas disease can cause several complications, such as Chagas cardiomyopathy, the most severe clinical form of the disease. Chagas cardiomyopathy is complex and involves biological and psychosocial factors that can compromise health-related quality of life. However, it is necessary to establish interactions that significantly impact the health-related quality of life of this population. Therefore, we aimed to develop and present a theoretical model on the impact of Chagas cardiomyopathy on the health-related quality of life of patients. Methods: This is a cross-sectional study with a multi-methodology approach. The model's development process relied on the findings of a systematic review of qualitative studies, as well as a qualitative study involving participants from original communities, conventional rural areas and urban centres. Patients diagnosed with Chagas cardiomyopathy were interviewed using a semistructured research script, and the sample size was determined by theoretical saturation. Ultimately, the model underwent evaluation and received approval from three specialists in Chagas cardiomyopathy. Results: Patients experience many emotional conflicts, manifested by feelings of sadness, existential emptiness and anxiety. They have fears related to the course of the disease, the inability to care for the people they love, their suffering and that of the family caregivers, as well as the fear of invasive treatments and death. The model based on social determinants of health was created and presented three different levels of factors that impact patients' health-related quality of life. At the first and most external level are social, cultural and environmental conditions: absence from work, difficulties in accessing healthcare services, limited resources for specialised care and geographical barriers to accessing healthcare services. At a more internally committed level, there are social factors and community networks encompassing social isolation, family conflicts, social stigma, emotional aspects, fears and disabilities. The innermost layer of factors represents personal and behavioural complaints, such as physical ailments and poor sleep quality. Conclusion: The factors that affect the health-related quality of life of patients with Chagas cardiomyopathy are diverse in their biopsychosocial nature.