To accomplish the transition towards a sustainable growth, it is imperative to adopt modern value chain approaches within circular bioeconomy concepts. On this basis, the implementation of a biorefinery approach for wastewater valorization and simultaneous production of high-value market bio-products addresses major global challenges, thus, yielding significant environmental, economic, and social benefits. In this work, a methodological framework for the sustainability assessment of a holistic biorefinery approach for the inclusion of the environmental and socio-economic effects of wastewater valorization into new value chains, processes, and products is introduced. The proposed methodological framework is built upon a Life Cycle Thinking concept and design. More specifically, it includes three distinct pillars: (i) the environmental pillar, that maps the environmental impact of the whole supply chain of wastewater utilization for the production of high added-value products; (ii) the techno-economic that makes provisions for the feasibility and viability of  the entire  production chain; and (iii) the social pillar, that introduces the social acceptance and  understanding to the production and utilization of the proposed solutions.  The core outcomes shed light on the potential of circular systems targeting sustainable and efficient wastewater valorization and application of the end-products from an economic, environmental, and social point of view.