Healthcare services and spaces are recognized as complex ecosystems where different user categories interact daily facing often urgent and difficult situations that challenge the established organizational and procedural models. The increasingly evolving needs and conditions influencing the processes affect the capacity to quickly adapt the available operational models as well as spaces to provide a timely and efficient response. This calls for new approaches and methods to enable the managing staff to overcome the conventional silos-based structure and integrate new methods and tools to facilitate interdisciplinary analysis and synergies. Some frontrunning healthcare structures started to adopt Service Design practices, which are largely grounded in the Design Thinking approach, to reshape the conventional models for improving the quality of user experience with remarkable expected impacts on social, economic, and environmental sustainability in the mid-long run. Following the rigorous investigation structure of Systemic Review, the paper explores the adoption of Service Design practices in frontrunner experiences focusing on organizational aspects to draft a reference framework, including successful factors, barriers, and viable pathways, which are currently missing. The main scope of the paper is accordingly to address the detected gaps in clarifying methods tools and goals of Service Design-oriented practices for improving healthcare processes and user experience quality. The main reported findings highlight the importance of introducing Co-Design and participative practices to integrate specialistic perspectives and organizational aspects as well as to engage all the key players at different levels.