Abstract Technological, demographic, epidemiological, environmental and social changes require investment in new sustainable hospital infrastructure; there is a lack of guidelines and interaction between Stakeholders. In February 2022, the Joint Research Platform Healthcare Infrastructures (JRP HI) was established consisting of Hospital Strategic Directions and Industrial Partners in Italy. Starting from the WHO Techincal Brief “Hospitals of the Future”, a national survey was carried out via web-survey and semi-structured interviews with a sample of 30 stakeholders to collect the main drivers and constraints for innovation and the framework from a One Health perspective and in terms of sustainability. The main needs to be addressed through the guidelines refer to digitalization (27%), flexibility (32%), environmental sustainability (36%) and economic sustainability (27%) as well as flow management (18%) and hospital infection (14%). The participants consider SDG-3 ‘Good Health and Wellbeing’ to be the most relevant for development activities. Hospital managers prioritize SDG-8 ‘Decent Work and Economic Growth’ (23%); vice-versa the industrial partners suggest SDG-11 ‘Sustainable Cities and Communities’ and SDG- 13 ‘Climate Actions’ (32%) as topics to be addressed. Furthermore, 57% of the respondents state that they lack adequate training, budget or leadership to apply innovative strategies in the day-to-day management of the healthcare organization. The survey highlighted a lack of initiatives, budget, and standardization for enhancing environmental sustainability in healthcare infrastructures. The sustainability of building systems depends on factors such as energy consumption, alternative energy sources, thermal comfort, water usage, waste management, ventilation, lighting efficiency, air quality, and construction materials. Ensuring the adoption of monitoring systems and harmonized standards of performance measurement is crucial for increasing the environmental sustainability.