The perception of sewage sludge has increasingly changed from being a waste, which is a burden to the environment and society, to a useful resource of materials and renewable energy. There are several available technologies at different stages of maturity that aim to convert sludge to energy in the form of electricity and/or fuels. In this paper, a decision-making support tool is proposed to help in choosing the optimal pathway for the sludge-to-energy conversion from a techno-economic perspective. The conversion technologies under study are: (1) anaerobic digestion, (2) pyrolysis, (3) gasification, (4) incineration, (5) supercritical water oxidation, (6) supercritical water gasification, as well as the corresponding dewatering and drying methods for each technology. Different synergies between the available technologies are compared by the formulation of a superstructure optimization problem expressed in a mixed-integer non-linear program (MINLP) model. The applicability of the proposed model is explored via a case study for a hypothetical sludge treatment plant with a capacity of 100 tons of dry solids (tDS) per day. The model is solved via the BARON solver using GAMS software within a reasonable processing time. According to the obtained results, the fast pyrolysis technology, coupled with filter press dewatering and thermal drying as pre-treatment steps, show the most promising outcomes with the minimum treatment cost of USD 180/tDS. Fast pyrolysis converts the sludge to bio-oil, which can be used as an alternative fuel after further refining, and biochar, which can be used for soil amendment or adsorption purposes. The model parameters are subject to uncertainty that is addressed in the sensitivity analysis section of this paper. Moreover, the pyrolysis pathway shows a high degree of robustness in most of the sensitivity analysis scenarios. Meanwhile, anaerobic digestion coupled with fast pyrolysis demonstrates the best energy recovery performance upon increasing electricity prices.