BackgroundHealthcare systems worldwide face unprecedented challenges, including rising healthcare costs, aging populations, increasing chronic disease burdens, workforce shortages, environmental concerns, and health inequities. Sustainable healthcare systems are essential for ensuring long-term access to quality healthcare services while balancing economic, social, and environmental responsibilities.ObjectiveTo evaluate the key determinants of healthcare sustainability and identify strategies for building resilient and efficient healthcare systems in the 21st century.MethodsA cross-sectional analytical study was conducted among 1,500 healthcare professionals, policymakers, hospital administrators, and public health experts. Data were collected using structured questionnaires assessing perceptions of healthcare sustainability, resource utilization, environmental responsibility, healthcare accessibility, and system resilience. Descriptive statistics and multivariate logistic regression analyses were performed.ResultsParticipants identified healthcare financing (82.7%), workforce development (79.8%), digital health integration (76.5%), environmental sustainability (71.2%), and equitable healthcare access (84.3%) as critical pillars of sustainable healthcare systems. Institutions implementing sustainability initiatives reported improved resource efficiency and patient outcomes.ConclusionSustainable healthcare systems require integrated approaches that combine financial resilience, workforce strengthening, environmental stewardship, technological innovation, and equitable healthcare delivery. Strategic policy reforms and investment in sustainable healthcare infrastructure are essential for future health system resilience.