Background: In the dynamic healthcare landscape, organizational agility is crucial for adapting to evolving demands, fostering work engagement, and enhancing readiness for change among staff nurses. Aim: This study aimed to investigate the relationships between organizational agility, work engagement, and readiness for change among staff nurses in a tertiary care hospital. Methods: A descriptive correlational design was employed, guided by the STROBE guidelines. Involving 305 staff nurses from Beni-Suef University Hospital, Egypt. Data were collected using validated surveys assessing organizational agility, work engagement (UWES), and readiness for change. Statistical analyses included Descriptive statistics, Pearson’s correlations and multiple linear regression. Results: Total organizational agility showed strong positive correlations (p < 0.01) with all subdimensions, ranging from (r = 0.702 to r = 0.896). Work engagement and its subdimensions (vigor, dedication, absorption) demonstrated strong positive correlations with each other ranging from (r = 0.871 to r = 0.912), Readiness for change displayed weak to moderate positive correlations with organizational agility and work readiness subdimensions. The table also includes mean and standard deviation values for each variable. Organizational agility and readiness for change significantly predicted work engagement, with readiness having a stronger impact. Conclusion: Organizational agility and readiness for change are vital predictors of work engagement, and the management of resource flexibility requires careful consideration. Cultivating agile environments, fostering shared leadership, and prioritizing employee engagement are essential for enhancing nurses’ adaptability and improving healthcare outcomes.