We propose optimization-based approaches for distillation network synthesis and heat integration, which can contribute to finding more energy efficient and sustainable chemical systems. For distillation network synthesis, we first propose unit models for distillation: 1) versatile shortcut distillation column and 2) separation energy targeting models. The models are to address systems where the components that are present in the feed can vary due to zero flow rates of some components, which naturally appear in process synthesis problems. The distillation column model can calculate component distributions and the energy requirement for a desired distillation task. The separation energy targeting model can be used to estimate an energy requirement target for the separation of a mixture without finding detail network configurations. We also propose a generalized superstructure-based distillation network synthesis model with improved modeling capabilities. The model can assign multiple mixtures to be separated to different columns of the network while considering interactions between separation steps for each mixture. In terms of outlets, products with general specifications, including pure components and multi-component mixtures, as well as streams without strict specifications (e.g., reactor recycle streams), can be readily handled. Stream bypass and thermal coupling are simultaneously considered to find more energy efficient configurations. In addition, we propose an approach to leverage graphical insights in the optimization-based distillation network synthesis, where graphically inspired feasibility constraints are combined with a superstructure-based approach. For heat integration, we propose utility targeting and heat exchanger network synthesis models that account for variable stream temperatures and flow rates, as well as unclassified streams. Even with the extended capabilities, the model remains linear using discrete temperature grids, leading to a more tractable optimization model. The proposed model is well suited to problems where process configurations and the associated heat exchanger network are simultaneously synthesized. Several extensions areproposed, including nonisothermal mixing and phase changes.