Background: Assessing the burden of the most common types of cancer, including breast cancer, is one of the main health research priorities in the Sultanate of Oman. Family caregivers perform many activities that were previously performed by health professionals. Due to the rising incidence of breast cancer and the shorter length of hospital stays, more pressure is being placed on family members to take care of their close relatives who are ill. However, studies that investigate caregivers' burdens in Middle Eastern countries, including Oman, are limited. Aim: The main aims of the study were to describe the levels of burden, social support, and self-efficacy among family caregivers of women with breast cancer, as well as the relationship among these variables. In addition, the study aimed to examine the relationships of the burdens to the selected medical and sociodemographic variables of patients and caregivers. Method: The study employed a descriptive cross-sectional design to describe the level of burden, the social support, and the self-efficacy among family caregivers. The Zarit Burden Interview (ZBI), the Multidimensional Scale of Perceived Social Support (MSPSS) and the General Self-efficacy (GSE) scale were used to measure the levels of the three variables. The family caregivers were recruited from two leading hospitals in Oman, namely the Sultan Qaboos University Hospital and the Royal Hospital. Results: The caregiver burden was low (M = 15.89, SD = 12.89). More than half of the participants reported a high level of perceived social support (M = 5.14, SD 1.49) and self efficacy (M = 3.03, SD = 0.52). The high burden was associated with the age of the caregivers and the relationship of the caregiver to the patient. In addition, family subscales for social support (r = − 0.181, p = 0.043) and self-efficacy (r = - 0.266, p = 0.011) were negatively associated with burdens. Conclusion: The results emphasized the need for health professionals to conduct early assessments to identify caregiver burdens, and to consider both patients and their caregivers when establishing management strategies. The findings also emphasized the role of family support and self-efficacy in reducing family caregivers' burdens, thus indicating the need for more strategies at the community level to ensure that caregivers are receiving the required support that can help to decrease their burdens as caregivers.