The objective of this paper is to present a generic and systematic methodology for identifying the feasible retrofit design alternatives of any chemical process. The methodology determines a set of mass and energy indicators from steady-state process data, establishes the operational and design targets, and through a sensitivity-based analysis, identifies the design alternatives that can match a set of design targets. The significance of this indicator-based method is that it is able to identify alternatives, where one or more performance criteria (factors) move in the same direction thereby eliminating the need to identify trade-off-based solutions. These indicators are also able to reduce (where feasible) a set of safety indicators. An indicator sensitivity analysis algorithm has been added to the methodology to define design targets and to generate sustainable process alternatives. A computer-aided tool has been developed to facilitate the calculations needed for the application of the methodology. The application of the indicator-based methodology and the developed software are highlighted through a process flowsheet for the production of vinyl chlorine monomer (VCM).