The adaptive reuse of cultural heritage contributes to heritage conservation, leveraging on the heritage potential to enable sustainable development and enhance urban livability. Yet, it is seldom applied as intervention. This research furthers the knowledge on the challenges to the adaptive reuse of cultural heritage. Through the case study of Salerno (Italy) and a participatory methodology, this research organized a stakeholder engagement workshop, facilitating the interaction of stakeholders—representing the public, private, civic, and knowledge sectors, while using a theoretical framework based on the six steps of the UNESCO Historic Urban Landscape approach to adopt a multi-scale perspective. The content analysis of the data reveals 55 themes encompassing challenges and solutions. These themes are presented in a general overview, followed by an in-depth reporting of the five most discussed themes, i.e. knowledge production and management, participation, valorization, approaches, and cooperation. Besides the contribution to science, this research also offers an overview of challenges and possible solutions for prospective stakeholders in the adaptive reuse of cultural heritage, informing future decision- and policy-making activities towards greater sustainable development within the built environment.