Home care nurses have become the main references in home care for vulnerable patients. In patients’ homes they offer comprehensive and continuous care to both the vulnerable population and their families. The aim of this qualitative study was to explore experiences and perspectives of home care nurses regarding the care of vulnerable patients in Spain. We conducted in-depth semi-structured interviews with 15 home care nurses working with a vulnerable population. From a data analysis, two themes and four subthemes emerged: (1) “barriers to providing home care to vulnerable populations”, with the following subthemes: “the particularities of the patient and their home caregivers” and “perceived barriers for the involvement of home care nurses in the care”; and (2) “the emotional cost of home care” with the subthemes “home care is draining for caregivers” and “the impact of home care on the home care nurses”. These findings show us that nurses face a number of difficulties in home care for vulnerable patients. The training of nurses in certain competencies and skills by the social health services would enhance the quality of care offered to these patients.