The need to achieve a sustainable process performance has become increasingly important in order to keep a competitive advantage in the global markets. Development of comprehensive and systematic methods to accomplish this goal is the subject of this work. To this end, a multi-level framework for techno-economic and environmental sustainability analysis through risk assessment is proposed for the early-stage design and screening of conceptual process alternatives. The alternatives within the design space are analyzed following the framework's work-flow, which targets the following: (i) quantify the economic risk; (ii) perform the monetary valuation of environmental impact categories under uncertainty; (iii) quantify the potential environmental risk; (iv) measure the alternatives' eco-efficiency identifying possible trade-offs; and, lastly (v) propose a joint risk assessment matrix for the quantitative and qualitative assessment of sustainability at the decision-support level. Through the application of appropriate methods in a hierarchical manner, this tool leads to the identification of the potentially best and more sustainable solutions.2 Furthermore, the application of the framework is highlighted by screening two conceptual glycerol bioconversion routes to value-added chemicals namely 1,3-propanediol (1,3-PDO) and succinic acid.