Background: Raising climate change awareness at the local level is critical as climate change impacts are exacerbating the number and extent of disasters in this disaster-prone country. So, nurses have a role to coach and inspire the public to play a role against climate change. This study aimed to evaluate the effect of instructional guidelines regarding climate change on nurses' knowledge and its relation to environmental sustainability practice. Design: A Quasi-experimental research design one group pre & post-test was utilized. Setting: The current study was conducted in Port Said Hospital. Data were collected from Medical, Surgical, Critical Care Units, Obstetrics and Gynecology Unit Affiliated to Port Said Hospital. Sample: A convenient sample of nurses who were working at the previously selected units in the hospital constituted the study sample who agreed to participate in the study at the time of data collection. Tools: Tool (I): A structured interview questionnaire and Tool (II): Environmental sustainability practice questionnaire. Results: showed that the majority of the nurses had little to no background information about climate change and their main sources of information were social media. The study also revealed that there was a significant difference in the nurses' knowledge and practice of climate change before and after implementing instructional guidelines. Additionally, the study found that there were significant differences in the student's knowledge and environmental practices before and after the implementation of instructional guidelines. The results also showed a positive correlation between knowledge and practice scores. Conclusion: Instructional guidelines implemented regarding climate change have a positive effect on improving nurses' knowledge and environmental sustainability practice. Recommendations: Develop workplace green teams, influence workplace practices, and policies, and educate patients and families on climate change and health to help provide care that is climate and environment-friendly. Establish strategies to encourage environmental sustainability in the workplace. In addition, the development of educational strategies to make nurses more aware of the importance of sustainability in nursing practice to mitigate the impact of climate change.