Steam explosion pretreatment was developed and evaluated to remove pharmaceuticals and heavy metals from wastewater sludge and to improve its biodegradability and methane yield. Effects of pressure (5-15 bar) and duration (1-15 min) during the pretreatment were examined, and the pretreatment efficiency was evaluated based on the solubilization degree, the capillary suction time (CST) test and anaerobic digestion. The removal efficiency of ibuprofen, acetaminophen, and amoxicillin was 65%, 69%, and 66% and 70%, 66%, and 70% in primary sludge (PS) and waste-activated sludge (WAS), respectively. The highest percent release efficiency of heavy metals, i.e., lead, cadmium, and silver, for PS and WAS was 78%, 70%, and 79% and 79%, 80%, and 75%, respectively. The highest methane yield was obtained after pretreatment at 10 bar for 15 min and at 15 bar for 10 min, with respective yields of 380 and 358 mL CH4/g volatile solids (VS) for the PS and 315 and 334 mL CH4/g VS for the WAS. The results of methane production indicated that the decreased concentrations of pharmaceuticals and heavy metals resulted in increased biodegradability of PS and WAS. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).