BACKGROUND The European Health Data Space Regulation is a European Union (EU) initiative aimed at promoting the sharing and safe use of health data across the EU. Its creation is based on the European Digital Strategy for Data (EC). COM/2020/66) and allows the European Community (EC) to fulfil its objectives of improving public health, reducing health inequalities, and promoting a more social Europe. OBJECTIVE To summarise the available scientific evidence on the application of the European Health Data Space Regulation and identify the primary challenges and successes of its implementation Europe. METHODS A comprehensive literature search conducted on May 22, 2025, identified 321 references. After removing 149 duplicates, 172 records remained for the title and abstract screening. Of these, 68 were excluded because they did not meet the study's inclusion criteria. The remaining 114 full-text articles were retrieved for a detailed assessment of eligibility. A total of 114 studies were assessed for eligibility. Data were extracted using a predetermined form, including various parameters such as author, year, and outcomes. RESULTS : A total of 45 studies were included in this review. Three overarching themes emerged: Governance and Regulatory Policies (45 studies), Technologies and Infrastructure (38 studies), and Stakeholder Participation (31 studies). As several studies addressed multiple themes, these categories are not mutually exclusive. The findings indicate that the successful implementation of the European Health Data Space (EHDS) hinges on the synergistic interaction among governance mechanisms, technological infrastructures, and stakeholder engagement. CONCLUSIONS These findings underscore the potential of evidence to the successful implementation of EHDS requires coordinated efforts to align policies, enhance interoperability, and address legal and security challenges. Clear governance, stakeholder involvement, and robust data systems are key to fostering trust and ensuring effective deployment. Despite these challenges, the EHDS holds great potential for enhancing healthcare and research through secure cross-border data sharing.