Within the goal of reducing greenhouse gas emissions and supplying sustainable energy, complex integrated energy conversion systems have to be designed by taking into account thermodynamic, economic and environmental considerations simultaneously. The process performance highly depends on the quality of the process integration and on the energy conversion, in particular, on how the heat requirements are balanced and how the combined heat and power generation is integrated. In chemical processes, the heat requirements after heat recovery are typically satisfied by the energy conversion system, while for fuel and electricity producing processes, the requirements are balanced by waste and process streams available on-site. The optimal internal heat recovery and utility integration can be computed by applying heat cascade models that are solved by using mathematical programming techniques. The mass and energy balances of the process unit operations are therefore satisfied by the optimal energy conversion system integration without having to explicitly model the heat exchanger network. The presented thermo-economic optimization approach combines flowsheeting and process integration techniques with economic evaluation and life-cycle assessment in a multi-objective optimization framework. The advantage of including the process integration model in the design process is that the influence of the process design and operation is reflected on the thermo-environomic performance of an energy balanced system in which the heat supplied from energy resources is integrated. The methodology has been successfully applied to study CO2 capture concepts in power plants using natural gas, coal or biomass resources, to analyse thermo-chemical H2 production processes and to evaluate different biofuel processes producing Fischer-Tropsch fuel, methanol, dimethylether and H2 by biomass gasification. The potential performance improvement through process integration is revealed for each case. In particular, it is highlighted how the optimization of the combined cycle valorizing the excess heat and of heat pumping options improve the process efficiency by simultaneously maximizing the combined production of fuel, captured CO2, heat and power. This shows that this computer-aided process design strategy combining flowsheeting, energy integration, cost assessment and multi-objective optimization is a powerful tool to systematically generate different process options, assess trade-offs and reveal process improvements through process integration.