BackgroundScholars are undermining the empowerment of holistic nursing care competence in developing countries like Ethiopia, compromising the care provided by competent nurses in clinical areas.ObjectiveTo assess holistic nursing care competence and associated factors among nurses working in the Government Hospitals of South Wollo Zone, Northeast Ethiopia, 2022.MethodsAn institutional-based cross-sectional study design was carried out involving 446 nurses. A random sampling technique was employed to select participants, and a self-administered questionnaire was utilized. The data were coded, entered into Epidata version 4.6.0.2, and subsequently exported to the Statistical Package for Social Science version 27 for analysis. The findings were summarized using tables. Linear regression model analysis was implemented and variables with p-values less than 0.05 were identified as significant predictor variables.ResultsThe mean score of staff education and management, ethical-oriented practice, general aptitude, and nursing care in the team and professional development domains of holistic nursing care competence were 3.8 +/- 1.3 (3.7-3.9),4 +/- 1.4 (3.9-4.2), 4.2 +/- 1.3 (4-4.3), 4 +/- 1.4 (3.8-4) and 3.9 +/- 1.5 (3.7-4) respectively. Being female, having frequency of training, being single, working primary hospital, having workload, and being staff had a positive relationship with holistic nursing care competence domains, whereas poor job satisfaction, age and low self-efficacy had a negative relationship with holistic nursing care competence domains.ConclusionStaff education and management, ethical-oriented practice, general aptitude, nursing care in the team, and professional development domains of holistic nursing care competence mean scores were recorded low. Therefore, the hospital managers and other responsible bodies should pay special attention to empowering nurses by enhancing their management capacity, fostering team care, promoting professional growth, improving problem-solving capacity, ensuring compliance with nursing ethics guidelines, focusing on staff motivation, and boosting their professional confidence.