This study presents a novel framework that examines the integration of Policies, Institutions, and Regulations (PIR), uncovers existing gaps, and provides insights into policy implementation, to enhance wastewater reuse practices. The research aims to answer two key questions: 1) What are the barriers to PIR alignment that hinder the advancements of wastewater reuse; 2) which reforms can be prioritized according to their “implementability”? Using Portugal as a case study, this research demonstrates the framework's applicability in identifying and navigating the complexities of policy, institutional roles, and regulatory environments that influence wastewater management. The study employs a comprehensive analysis that combines PIR insights with gap analysis and ambiguity and conflict analysis. The proposed framework allows to explore the systemic constraints and proposes a set of actionable reforms. In the case study of Portugal, the reforms aim to leverage economic incentives, such as restructuring abstraction and discharge fees and introducing fiscal benefits, while advocating for technological innovations to improve water treatment efficiency. Emphasizing household wastewater connectivity further highlights a pathway towards achieving economic and environmental sustainability in water utilities. By applying this framework to the Portuguese context, the research demonstrates its potential to guide policymakers and stakeholders in designing effective strategies for a wider adoption of wastewater reuse and illustrates the adaptability and relevance of the framework in different settings.