Evidence suggests that healthcare professionals should provide supportive care to cancer patients to address their informational, practical, emotional, and psychosocial requirements, therefore Symptom Navi program is a nurse-led program that helps patients with cancer better control their symptoms. The aim of the current study was to evaluate the effect of implementing the Symptom Navi© program on outcomes for patients with cancer. A quasi-experimental research design was applied to two groups (study & control), Sample: purposive sample120 patients for each group were selected from the outpatient clinic of Mansoura Oncology Center, Egypt. Five tools were used to gather data: The Demographic and patients' medical history datasheet, The Monroe Dunaway Anderson Symptom Inventory, the Self-Efficacy for Managing Chronic Diseases 6-item Scale, the Single-Item Linear Analog Scale Assessment (LASA), and the patient-reported chemotherapy indicators of symptoms and experiences. Results: The mean scores of MDASI and symptoms interfere with life of the study group decreased significantly (73.23 & 33.1) in posttest compared to (101.28 & 44.3) respectively in pretest (p < 0.001). There were also highly significant statistical differences in mean scores of self-efficacy and LASE scores of the study group (18.26 & 20.83 in pretest) instead of (28.68 & 22.39 in posttest). Conclusion: Implementation of the symptoms Navi program had a significant impact on reducing the severity of symptoms experienced by patients with cancer, promoting self-efficacy, in addition to enhancing the patient-reported chemotherapy indicators of symptoms and experiences, thus enhancing the overall quality of life, that can be adopted as a standard model of care. Recommendations: The SN©P is recommended to be applied within daily routines care and self-management implementation of patients with cancer.