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Hydrothermal treatment (HT) is a promising technology to enhance anaerobic digestion (AD) of municipal sludge. However, the capacity of pre‐ and inter‐stage HT (i.e., HT‐AD and AD‐HT‐AD, respectively) to enhance the digestibility of municipal sludge has not been sufficiently explored. This study compared the efficacy of pre‐ and inter‐stage HT performed from 90 to 185°C to enhance methane production from a mixture of primary sludge and waste activated sludge using mesophilic (35°C) biochemical methane potential tests. In both configurations, sludge solubilization increased with HT temperature. HT‐AD, and to a greater extent AD‐HT‐AD, increased the release of ammonium nitrogen. Even though HT at 185°C dramatically increased sludge solubilization, the overall specific methane yield with HT at 185°C was lower than or comparable to that at lower HT temperatures in the HT‐AD and AD‐HT‐AD configurations, respectively. Up to 155°C HT, the overall specific methane yield with the HT‐AD configuration was higher by 4.9%–8.3% compared to the AD‐HT‐AD configuration. However, when the HT energy was considered, compared to the control (i.e., AD of sludge without HT), the net energy gain (ΔE) decreased as the HT temperature increased, becoming negative at an HT of 185°C. The AD‐HT‐AD configuration resulted in a higher overall volatile solids destruction (by 8.1 to 20.1%). In conclusion, for municipal sludge with a relatively high ultimate digestibility, as was the case in this study, HT‐AD is preferable as it has a smaller footprint and is easier to operate than the AD‐HT‐AD configuration. However, given the significantly higher volatile solids destruction in the AD‐HT‐AD configuration, compared to the HT‐AD configuration, AD‐HT‐AD may be more beneficial considering post‐AD sludge handling processes.