Background: Women after mastectomy may experience unique stressors related to loss of femininity, changes in various social roles, body image, sexual concerns, and altered relationships with significant others. These problems eventually alter their coping strategies. The purpose of the study was to investigate the effect of nursing intervention on coping strategies of women after mastectomy. Method: A quasi-experimental research design (study & control groups' pre/post-test) was utilized. A purposive sample of 100 women after mastectomy was chosen. The study was conducted at the Female Surgical Department, Oncology Clinics of Menoufia University Hospital, Shebin El-Kom Teaching Hospital, and Oncology Hospital in Menoufia Governorate. A structured interviewing questionnaire, an observational checklist, and an adaptive coping strategies questionnaire were used. Results: The majority of the study group (86.0%) had a high coping level after the intervention compared to none in the control group. Also, there was a highly statistically significant improvement in the level of coping among the study group from 4% before the intervention to 86% after the intervention. Conclusion: The nursing intervention resulted in an improvement of total knowledge and practice scores related to breast self-examination. Also, there was a highly statistically significant improvement in all aspects of women's coping strategies in the study group compared to the control group. Recommendations: Women who have had a mastectomy are advised to receive ongoing knowledge and skills regarding adaptive coping strategies. Maternity nurses should be encouraged to participate in psychotherapy nursing interventions specialized for enhancing the coping skills of women with mastectomy.