In many countries, the consent of family members is required for organ donation from brain-dead patients who are potential candidates for organ donation. In this regard, knowing the factors affecting family members' decision for organ donation can help improve the conditions. This qualitative study aimed to identify the factors affecting family members' decision-making regarding donation of brain-dead patients' organs. This research applied qualitative research by focusing on the content analysis approach. The study started from April 2021 in Al-Zahra Hospital in Isfahan and Ayatollah Kashani in Shahrekord and continued until data saturation was reached (September 1401). Participants were assigned to one of three groups: brain-dead patients' family members who consented to organ donation, brain-dead patients' family members who declined to consent to organ donation, and people involved in the organ donation process. The sample was selected using the purposive sampling method. The data were collected using unstructured interviews and the field survey method. In this study, a qualitative content analysis with a contractual approach was used to analyze the data. The analysis of the collected data using different methods yielded 11 main categories, including 1) unresponsive healthcare system, 2) inadequate support from government systems, 3) weakness of social work organizations, 4) fear of being stigmatized, 5) cultural values, 6) symbolization, 7) perpetuation and the society's attitude, 8) development of personality system and generalism, 9) human values, 10) spiritual maturity, and 11) belief-religious challenges, leading finally to three themes, including 1) structural and functional weakness of systems, 2) sociocultural factors, and 3) worldview. The findings of the present research were able to identify the roots and social factors affecting Iranian families' decisions regarding the consent or nonconsent of brain-dead patient members. Health system administrators and organ donation committees in medical sciences universities in Iran can try to solve the shortage of donated organs by using the specific social aspects introduced in this study. It is also recommended to design effective models for more satisfaction of family members for brain death patient organ donation in healthcare based on the underlying concepts of this study.