Background: Breast cancer and its treatment lead to physical and psychological problems. So, nurses are responsible to identify patients' needs, then identify the appropriate nursing diagnosis and initiate plans for care based on such needs. Aim: To evaluate the effect of educational nursing program on performance and self-efficacy of females undergoing mastectomy. Patients and Methods: A quasi-experimental research design was utilized in this study. It was conducted in the general surgery wards, and follow up was carried out in oncology and general surgery out patient clinics at Assiut University Hospital and South Egypt Cancer Institute. A convenient sample of sixty adult female patients undergoing mastectomy, their ages ranged from 20 to 65years old . Patients were divided into two equal groups (study and control) thirty patients for each. Tools: Three tools were utilized in this study for data collection; Tool (I): Knowledge assessment questionnaire, Tool (II): Observation checklist, and Tool (III): General self-efficacy scale. Results: A highly statistically significant improvement was found in the study group regarding their performance and self efficacy post-program implementation than pre-program with P-value <0.001**. Conclusion: Application of educational nursing programs had a positive effect on performance and self-efficacy of females undergoing mastectomy. Recommendations: distribution of the educational booklet in the general surgery department and clinic for females undergoing mastectomy based on their needs assessment to improve their outcomes.