Background <p>The expansion of nurses’ career competencies and their capacity to adjust to changing healthcare needs are significantly influenced by effective leadership. Strategic flexibility helps nurses improve patient care outcomes, advance professional development, and acquire critical skills by creating a dynamic and responsive work environment.</p> Aim <p>To investigate the association between leadership practices and nurses’ career competencies and strategic flexibility’s role as an intermediary in this relationship.</p> Design <p>A descriptive cross-sectional study design was used, adhering to STROBE principles.</p> Methods and tools <p>Information was gathered from 400 nurses who worked in an Egyptian general hospital namely; El-Rahmania Hospital through structured questionnaires: the multifactor leadership questionnaire, the career competencies questionnaire, and the strategic flexibility questionnaire.</p> Results <p>Interpreting the discoveries of this study, a significant direct effect (Estimate = 0.089, <i>p</i> = 0.026) between leadership behaviors and strategic flexibility. This suggests that strategic flexibility is positively influenced by leadership. Moreover, leadership behaviors have a significant direct influence on career competencies (Estimate = 0.128, <i>p</i> &lt; 0.001), indicating that effective leadership directly enhances career competencies. Furthermore, A significant indirect effect (Estimate = 0.142, <i>p</i> = 0.002) is found in the relationship between strategic flexibility and career competencies, indicating that enhancing strategic flexibility enhances the impact of leadership on career development.</p> Conclusion <p>The statistically significant relationships between leadership practices, the nurses’ career competencies, and strategic flexibility show how interconnected they are. According to the findings, strategic flexibility significantly mediates the connection between competent nursing practice and effective leadership.</p> Nursing implications <p>The study’s conclusions have important ramifications for healthcare policy, leadership development, and nursing practice. Effective leadership techniques that encourage strategic adaptability can equip nurses with the knowledge and abilities needed to successfully negotiate challenging and quickly evolving healthcare contexts. Nurse leaders may increase job satisfaction, lower burnout, and boost retention rates by encouraging resilience, problem-solving skills, and ongoing learning. Additionally, healthcare organizations may guarantee better patient care, more efficiency, and a more engaged nursing workforce by placing a strong priority on strategic flexibility and leadership training.</p>