Background <p>As artificial intelligence (AI) becomes an integral part of healthcare, nursing practice is rapidly evolving, requiring a deeper understanding of how nurses’ attitudes toward AI influence essential competencies such as creative self-efficacy and clinical reasoning competency, both of which are crucial for delivering safe and effective patient care.</p> Aim <p>This study aimed to explore the relationship between nurses’ AI-related attitudes, creative self-efficacy, and clinical reasoning competency.</p> Methods <p>A cross-sectional descriptive-correlational design was employed, involving a convenience sample of 380 nurses working in critical care units at a university-affiliated hospital in Egypt. Data were collected using three validated instruments: the Nurses’ Artificial Intelligence Attitudes Scale, the Creative Self-Efficacy Scale, and the Clinical Reasoning Competency Scale. Data analysis included both descriptive and inferential statistics.</p> Results <p>The majority of nurses demonstrated high levels of AI-related attitudes and clinical reasoning competency, while moderate levels of creative self-efficacy were observed. A strong positive correlation was found between AI attitudes and both creative self-efficacy and clinical reasoning competency (<i>r</i> = 0.559 and <i>r</i> = 0.728, <i>p</i> &lt; 0.001, respectively). Regression analysis confirmed that AI attitudes were significant predictors of both creative self-efficacy and clinical reasoning competency, explaining 37.4% and 56.5% of their variance, respectively. Additionally, educational qualifications and years of nursing experience were identified as significant factors influencing these competencies.</p> Conclusion and Implications <p>Positive attitudes toward artificial intelligence (AI) play a crucial role in enhancing nurses’ creative self-efficacy and clinical reasoning competency. Therefore, fostering positive perceptions of AI and providing targeted training are vital to prepare nurses for AI-integrated clinical environments. Integrating AI-focused content into nursing education and promoting continuous professional development are key strategies to strengthen nurses’ readiness to engage with AI-driven healthcare. Additionally, healthcare organizations and nursing leaders should create supportive environments that encourage AI adoption while preserving the principles of patient-centered care.</p> Clinical trial number <p>Not applicable.</p>