ABSTRACT Waste-activated sludge (WAS) generation is increasing due to the increased generation of wastewater owing to industrialization and urbanization. The disposal of WAS is a significant environmental and financial concern that can be offset by stabilization and valorization via anaerobic digestion (AD). However, the biodegradation is limited due to microbial cells and extracellular polymeric substances (EPS). Physical, chemical, biological, and hybrid pretreatments and the addition of accelerant materials for enhancing direct interspecies electron transfer (DIET) are among the strategies to overcome the poor biodegradation of WAS. Alkaline pretreatment disintegrates the floc structure of WAS by increasing the osmotic pressure, while microwave irradiation has thermal and a-thermal effects and increases the availability of organics for biodegradation. Moreover, the combination of alkaline and thermal pretreatments has synergic effects on solubilization, biogas production, and dewaterability. The disintegration of WAS is recognized by alteration in volatile solid (VS) content, sCOD, BOD/sCOD, turbidity, nutrients solubilization, dewaterability, particle size, specific surface area, change functional group, alteration in microorganism community, microorganism abundance, color, moisture content, lag phase, and biogas production. Higher doses of pretreatment increase COD solubilization but not biodegradable COD. Maximum COD solubilization ranged from 2 to 37% in alkaline, 21 to 260% in the microwave (MW), and 28 to 624% in hybrid pretreatments.