Background: Palliative care is an essential aspect of comprehensive cancer treatment, aiming to enhance patients' quality of life by addressing their physical, emotional, and psychosocial needs. As key caregivers, nurses play a vital role in providing this support, particularly for individuals in the advanced stages of illness. The current study aimed to evaluate the effect of palliative care program on nurses' knowledge, attitudes, and self-efficacy toward the care of cancer patients. Research design: A quasi-experimental research design was used to achieve the aim of the study. Sample: A convenience sample of 150 nurses working at Minia Oncology Center was divided into study and control groups. Study Tools: Tool (I): A structured interview questionnaire, including Part 1: demographic characteristics of the nurses and Part 2: assessment of nurses' palliative care knowledge using the 20-item Palliative Care Quiz for Nursing (PCQN). Tool (II): Nurses' attitudes toward palliative care were assessed using an 11-item tool, with 6 positive and 5 negative items. Tool (III): Self-efficacy toward palliative care was assessed using the 12-item Palliative Care Self-Efficacy Scale. Results: There was a significant improvement in nurses' knowledge, a positive shift in their attitudes toward end-of-life care, and enhanced self-efficacy in managing the complex needs of cancer patients. Additionally, significant positive correlations were found between nurses' knowledge, attitudes, and self-efficacy regarding palliative care in the study group after the educational program. Conclusion: The study concluded that the palliative care program positively impacted nurses' knowledge, attitudes, and self-efficacy toward palliative care among cancer patients. Recommendations: The study recommends continuous education in palliative care for nurses, integrating palliative care into nursing education programs, and distributing accessible Arabic booklets in oncology centers.