The aim of this study was to explore the experiences of Iranian family caregivers with regard to the burden of caregiving. This is in the context of illuminating and identifying the experiences of family members from different contextual perspectives. In this qualitative study, purposive sampling was conducted in 2016. Data were collected using semistructured interviews and were analyzed using content analysis. Data analysis identified 4 categories and 8 subcategories: (1) burnout (physical problems and psychoemotional stress), (2) role conflict (balancing caring roles and family responsibilities; failure in professional or educational roles), (3) health system tensions (inadequate support from health professionals; ignorance of family members in health structure), and (4) social challenges of cancer (economic burden; taboo of cancer). In conclusion, nurses need to provide individualized support and counseling that address the sources of burden. This highlights the benefit of training health care professionals to provide culturally sensitive support based on family caregivers' needs and circumstances.