This work proposes a novel methodology for the optimization of industrial waste-to-energy networks, combining logistic, site management, and process elements into a single mixed integer linear problem (MILP) formulation. The developed model is validated with real information stemming from industrial and institutional partners and consequently applied to a multisite case study covering the whole Swiss industrial waste-to-energy network. Due to the sparse nature of its chemical and pharmaceutical industry, and to centralized incineration facilities, this can be considered as an ideal case for testing the application of developed methodology to complex systems. A set of objective functions is used to investigate the implications of diverging goals on economic, environmental, and safety aspects, with particular focus on investments and possible synergies. Results indicate the importance of investments in oxy-combustion that, together with a more cooperative management of the network including the cement industry, enable a more local waste treatment with a consequent reduction of shipments.