As healthcare delivery, education, and technology dramatically evolve, middle managers serve a vital role in communication. Studies provide convincing evidence that resilience and self-directed learning can each be acquired and improved. This study investigated the relationship of resilience and self-directed learning readiness in healthcare middle managers. From a large, integrated healthcare system in Western Pennsylvania, 68 interprofessional middle managers participated. A significant positive correlation (p < 0.001) was found between the mean scores of the Self-Directed Learning Readiness Scale and the Personal Resilience subscales of Positive: Yourself, Positive: The World, Flexible Thoughts, and Focused. Approaches used to solve new problems in the workplace by highly self-directed, highly resilient healthcare middle managers were identified as conferences/workshops (40%), internet (20%), and colleagues/mentors (20%). It is imperative for healthcare middle managers to optimize their abilities and resources to engage employees, manage costs, and attain favorable, sustainable patient outcomes as transformations in healthcare continue in 21st-century healthcare delivery.