Implementation of e-health is expected to affect the outcomes of medical services positively, by contributing to the effectiveness and efficiency of overall healthcare ecosystem. This becomes more crucial in developing countries where access, finance, resources and competent professionals in healthcare are limited. This field study assesses healthcare professionals' insights, for the major challenges of ehealth development with a distinctive model and comparative analysis in four emerging countries; Turkey, Kingdom of Saudi Arabia, United Arab Emirates and Egypt. The research is conducted by user questionnaires and face to face interviews of healthcare professionals. Results indicate that information communication technology infrastructure, regulations, cultural and clinical adaptation of users, financing, supply chain management are some major challenges. Specially trust to e-business in healthcare, compliant use of big data in digital health and patient privacy play a key role for faster development of e-health.