Utilizing data collected from in-person interviews with cancer caregivers at a non-urban, southern site and an urban, northeastern site, the present study attempted to identify factors that account for multiple dimensions of caregiver subjective stress (i.e., emotional reactions to cancer care demands, such as feelings of exhaustion and fatigue, feelings of entrapment in care responsibilities, and loss of intimacy with the loved one suffering from cancer). Family caregivers of cancer patients were recruited from the Radiation Oncology, Outpatient, and Chemotherapy treatment centers at each site. The following inclusion criteria were applied: the participant must have indicated that she/he provided help to a loved one because of cancer and the participant must have considered themselves the person who provides the most help to the loved one suffering from cancer (i.e., primary caregiver). Following the screening procedure, the interviewer provided an informed consent form as well as necessary HIPAA documentation assuring the primary caregiver and patient of their rights as research participants and asked if they would be willing to participate in a 60–90 minute interview at a time and place of their convenience. These recruitment and interview procedures resulted in a cross-sectional sample of 129 cancer caregivers from the rural and 104 caregivers from the urban site, respectively. The protocol included three sections: 1) sociodemographic characteristics of caregivers and cancer patients (i.e., context of care), 2) primary objective stressors (i.e., care demands and cancer severity), caregiving resources (e.g., social support for the caregiver); and 4) primary subjective stressors (emotional distress experienced by the caregiver). All scales were averaged for the purposes of the analysis. A series of multiple regression equations was conducted, where the various indices of context of care, primary objective stress, and resources were regressed onto each dimension of primary subjective stress (i.e., role overload, role captivity, loss of intimate exchange). The final regression models accounted for a considerable amount of variance in role overload (R2 = .40), role captivity (R2 = .33) and loss of intimate exchange (R2 = .31). The most potent predictors of emotional distress in cancer caregiving were care demands, or care recipient behavior problems and activities of daily living care needs. Resources such as feelings of mastery over care responsibilities and socioemotional support from others appeared to alleviate feelings of distress on the part of cancer caregivers. The results emphasize the importance of informal family care provision in cancer, and how negative emotional outcomes can result due to these responsibilities. As opposed to cancer site or other variables (e.g., context of care), the most potent predictors of caregiver emotional distress appeared to lie in the behavioral and mood disruptions experienced by cancer patients, as well as any functional dependencies that occurred as a result of cancer. However, caregiving resources also played an important role in allaying negative emotional stressors; both intrapsychic (e.g., mastery) and external support (e.g., socioemotional support) were strongly and negatively related to feelings of exhaustion, emotional entrapment, or loss of intimacy. Overall, these results suggest the multifaceted nature of cancer caregiving stress, those factors that exacerbate emotional upheaval of caregivers, and how certain aspects of the cancer caregiving context can be bolstered to alleviate the negative ramifications of family cancer care. Overall, the findings have strong theoretical, clinical, and practice implications for the psycho-oncological literature