This paper presents a generic and systematic methodology for the generation of sustainable process alternatives with respect to new process design as well as retrofit design. The generated process alternatives are evaluated through sustainability metrics, environmental impact factors as well as inherent safety indices. The process alternatives for new process design as well as retrofit design are generated through a systematic method that is simple yet effective and is based on a recently developed path flow analysis approach. According to this approach, a set of indicators are calculated in order to pinpoint unnecessary energy and material waste costs and to identify potential design (retrofit) targets that may improve the process design (in terms of operation and cost) simultaneously with the sustainability metrics, environmental impact factors and the inherent safety indices. Only steady state design data and a database with properties of compounds, including, environmental impact factor related data and safety factor related data are needed. The application of the methodology is highlighted through the well-known HDA-process.