Background: The number of expatriate students has risen dramatically in recent years. Expatriate nursing students face unique challenges that might have a negative influence on their mental health, well-being, and academic performance. Aim: To assess the challenges facing expatriate nursing students at Cairo University and suggest guidelines to overcome these challenges. Design: A descriptive- exploratory design was utilized to fulfil the aim of this study. Setting: The study was conducted at the Faculty of Nursing, Cairo University. Sample: A convenience sample of 361 expatriate nursing students over a period of one month was included in this study. Tool for data collection: Challenges assessment questionnaire for expatriate nursing students, which consists of three sections: (1) Demographic characteristics of expatriate nursing students; (2) Challenges facing expatriate nursing students; and (3) Students suggested solutions for challenges. Results: Less than half of expatriate nursing students had moderate challenges, more than one-third had few challenges, and less than one-fifth of them had great challenges. A highly statistically significant correlation was found between all challenges' dimensions and total challenges. Conclusion: The most challenging aspects for expatriate nursing students were the academic challenges, followed by the clinical learning environment, and the nutritional challenges, then the sociocultural, psychological, financial, language, and communication challenges, and finally, the administrative challenges. Students suggested solutions to overcome these challenges were the presence of academic advisors for a limited number of students as well as using the English language in presenting the lectures from the faculty members. Recommendations: The current study recommended applying a sociocultural orientation program at the beginning of the educational program, aiming to raise students' awareness about the challenges that they may face, providing information about the available and needed resources, and lastly, providing periodic follow-up for their academic achievement by a selected group of the academic staff.