Biodiesel can be produced from a variety of feedstock. Oils from vegetable and plant sources have been commonly used as feedstock but other oil sources are also viable alternatives. Soybean, palm, sunflower, rapeseed, cottonseed, safflower, and canola oils are popular feedstock for current Biodiesel production plants. Animal fats, waste oils and even oils from microalgae are other renewable feedstock options for the transesterification of triglycerides to fatty acid methyl esters. With the current advances in research, the changing prices, and the supply, and demand of these feedstocks, there is a need to design flexible plants that can process various inputs. The objective of this work is to develop a systematic procedure for the design and operation of flexible biodiesel plants that can accommodate a variety of feedstocks. In particular, the proposed project will employ a holistic approach and a combination of process simulation, synthesis, and integration techniques. The developed simulation, integration, and optimization models along with the integrated experiments will provide a new platform that can systematically provide a complete strategy for innovative pathways for producing biodiesel. These new techniques will lay the foundations for fundamental research in the emerging area of sustainable biofuels. A case study is solved to demonstrate the merits and applicability of the devised procedure.