Chemical Process Sustainability, can be estimated using different sustainability indicators. The quantitative estimation of those indicators is necessary (i) for evaluating the environmental impact of a chemical process and (ii) for choosing the best design among different available alternatives. To accomplish these goals, the computerized calculation of sustainability indicators requires the use of at least three computer tools: (i) process simulation, (ii) molecular modeling and a. (iii) sustainability indicators software code. In this work, a complete software platform, Process Sustainability Prediction Framework, integrated with process simulation programs, which support the CAPE-OPEN interfaces, is presented and discussed. The article contains also description and application of molecular modeling techniques to estimate different toxicological data, which are used in the calculation of sustainability indicators. A representative example of one chemical process and thermo-physical properties used in the toxicological data calculation, are reported to demonstrate the applicability of the software to real cases. (C) 2009 American Institute of Chemical Engineers AIChEJ, 55: 1065-1078, 2009