Abstract Background: Rapid integration of Artificial Intelligence (AI) into healthcare is reshaping clinical practice, nurses must acquire updated knowledge and skills. Understanding nurses perceived challenges, and enabling factors is essential to ensure effective use of AI. Aim of the Study: Assess nurses’ knowledge, perceived challenges, and enabling factors related to the integration of AI in nursing at AlRajhy Hospital. Subjects and Methods: A descriptive correlational design was employed with a convenience sample of 280 nurses. Data were collected using a validated, self-administered questionnaire comprising three tools: the first assessed nurses personal and job characteristics data, and knowledge regarding AI in healthcare services; the second addressed perceived challenges; and the third focused on enabling factors supporting AI integration. Results: The findings revealed that 66.8% of nurses had a satisfactory level of AI knowledge. Ethical concerns ranked highest among perceived challenges 5.12 ± 0.88, while education and training emerged as the most significant enabling factor 23.88 ± 5.57. Significant associations were observed between knowledge levels and both perceived challenges (negative correlation) and enabling factors (positive correlation). Personal and job-characteristics such as age, education, and years of experience also had a notable impact on these relationships. Conclusion: Higher levels of knowledge were associated with fewer perceived challenges and greater recognition of enabling factors, emphasizing the importance of bridging the gap between challenges and enabler in AI integration within nursing. Recommendations: Structured AI training programs should be implemented, targeting new employed nurses or nurses with lower educational qualifications.