Deaths caused by cardiovascular diseases (CVDs) account for 60% of all deaths that occur in rural and remote areas. Disease management programs are increasingly used to improve the effectiveness of chronic care. Nurses are a key component of the health workforce and have an important role to play in CVD prevention, treatment, and the care of sick people in remote areas. Due to the nature of their work, nurses are prone to working hard, and to experience burnout, sleep, or eating disorders. This is often exacerbated by a shortage of staff and equipment. The objectives of the study were to explore and describe the experiences of professional nurses in managing CVDs in South African rural and peri-urban clinics. A qualitative, explorative-descriptive design and a contextual research approach were adopted for the present study. Purposive sampling was employed to recruit nurses who were managing patients with CVD from 11 primary health care facilities. Data were collected through semi-structured individual interviews and analyzed using Tesch's open coding method. Interview transcripts were coded and analyzed for common themes. The following two major themes emerged from the data: perceived institutional challenges affecting the management of CVDs and nurses' perceptions of patient challenges that impede the effective management of CVD. The study concludes by highlighting that apart from a resource challenge, the shortage of nurses in rural clinics is the biggest reason behind overcrowding, waiting long hours for consultations, and an increase in the workload, resulting in medical errors and poor quality care. It is, therefore, recommended that, for improved care and management of CVD in rural populations, local governments need to employ more skilled nurses whilst availing the necessary material resources.