Background: Professionalism and systems thinking play an important role in any health care institution as they shape and affect the nature of head nurses' knowledge, behaviors, skills and attitudes that contribute to deliver safe nursing care within the rapidly altering work environment. Aim: The present study aims to investigate head nurses' professionalism, systems thinking and its relation to safe nursing care at Oncology Center. Design: A descriptive correlational design. Setting: All  Oncology Center's inpatient units. Subjects: 110 head nurses for study sample. Tools: Data were collected by the use of nurses' professionalism inventory, systems thinking scale, and safe nursing care questionnaire. Results: The highest percent of head nurses showed high level of professionalism, systems thinking and safe nursing care (53.6%, 43.6%, and 55.5%) respectively. There was highly statistically significant positive correlation between safe nursing care with both head nurses' professionalism and systems thinking. Conclusion: There was highly statistically significant positive correlation between safe nursing care with both head nurses' professionalism and systems thinking. Recommendations: Provide safe environment that enhances head nurses' professionalism and systems thinking to enhance safe nursing care. Developing of training programs to increase head nurses' knowledge and skills related to systems thinking. Meeting regularly with head nurses in order to listen to them as well as foster their responsibility and accountability to provide safe nursing care.