A methodology for the design of intensified processes that includes economic, sustainability, and inherent safety factors is presented. Given an original synthesis problem to produce a desired chemical from a set of feedstocks, a base design is first generated from which a gradual intensification procedure is carried out until a fully intensified design with a minimum number of pieces of equipment is achieved. A novel approach in this work is that in addition to economic and sustainability factors, inherent safety metrics are evaluated at each step of the intensification methodology. In particular, the evaluation of inherent safety poses an important challenge because of the hybrid types of equipment units that inevitably appear as part of the intensification task. An adjusted FEDI index is included for such an evaluation as part of the methodology. Two case studies, one dealing with the production of isoamyl acetate and another one with the production of dioxolane products, are taken to show the applicability of the intensification methodology. It is shown that a fully intensified structure does not necessarily represent the best option when the three metrics are taken into account.