<![CDATA[The integration of electronic referral (e-referral) systems into healthcare ecosystems offers significant potential to enhance care coordination, reduce inefficiencies, and improve patient outcomes. However, challenges persist across legal, technological, and social dimensions. A PRISMA-based Systematic Literature Review (SLR) highlights jurisdictional barriers, such as GDPR-HIPAA mismatches, with 40% of EU organizations facing hurdles in sharing data with U.S. partners. Stringent data localization laws in countries like Russia and China further complicate interoperability. Ethical frameworks, including beneficence and non-maleficence, are critical for trust in sensitive care areas. Technological gaps include uneven HL7 FHIR adoption, infrastructure limitations, and underutilization of AI and blockchain innovations. Estonia’s X-Road system demonstrates blockchain’s role in reducing referral wait times by 30%, while India’s e-Sanjeevani platform serves remote areas offline. Clinician resistance and digital literacy gaps necessitate tailored solutions. Escalating cyber threats demand robust measures like zero-trust architectures. Public-private partnerships, open-source platforms, and measurable outcomes (?80% clinician adoption, <48-hour approval times) are vital. Pandemic-resilient systems and sustainable cloud solutions further emphasize scalability and equity. Harmonized policies and inclusive stakeholder engagement are essential for global success.]]>
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