Background: India’s health system is currently experiencing rapid change. Achieving India’s aspirations for improved population health and universal health coverage will require the contribution of all health providers; public, private-for-profit, not-for-profit, and charitable providers. Among the largest charitable providers in India are Christian mission hospitals, who have played a historic role in healthcare delivery to the poor and underserved. This study explored the main internal and external challenges facing mission hospitals, their response to those challenges, and the role they might play in the broader health system going forward. Methods: The study employed interdisciplinary methodology to assess the top challenges and responses between 2010-2017. The theory of everyday resilience was used to categorize challenges as chronic stresses or acute shocks and to explore features of resilience in responses to challenges, along with the underlying capabilities that enable resilience responses. Results and Discussion: Mission hospitals were impacted by social, political, and health system challenges. Most operated as “stressors,” for example, strained governance structures and human resource shortages. “Shocks” included major changes in health policy and increasing competition from for-profit providers. In response, some mission hospitals exhibited features of everyday resilience, traversing between absorptive, adaptive, and transformative strategies. Among mission hospitals that appeared to be successfully navigating challenges, three core capacities were present: 1) cognitive capacity, understanding the challenge and developing appropriate response strategies; 2) behavioral capacity, having agency to deploy context-specific responses; and 3) contextual capacity, having adequate resources, including hardware (e.g., money, people, infrastructure) and software (e.g., values, relationships, networks), to exercise the first two capacities. Building on their history and current examples of everyday resilience, mission hospitals can contribute to the larger health system by attending to health and well-being at the margins of society, encouraging innovation, developing human resources, and engaging in policy and advocacy. Conclusion: While mission hospitals face pressing internal and external challenges, many exhibit features of everyday resilience and retain strong commitment to population health and service to the poor. These features make them potentially strong actors in their local contexts as well as potential partners in the realization of improved population health across India.