Antonio J. Aragón-Barroso, Alejandro González‐Martínez, Jesús González-López, Francisco Osorio
• Industrial wastewater diversity challenges optimal EGSB operational conditions. • Operational conditions must be adjusted for each specific wastewater case. • Organic loading rate and upflow velocity are the most decisive factors influencing granulation. • Microbial communities adapt to influent and operational changes, sustaining performance. • Methanosaeta abundance indicates compact and stable granular biomass. Expanded granular sludge bed (EGSB) reactors have emerged as promising high-rate anaerobic treatment systems for industrial wastewater (WW) with increasing organic loads and complex compositions. This review provides a systematic overview of the main operational parameters, including organic loading rate (OLR), volatile fatty acids (VFA), pH, temperature, influent solids, upflow velocity (V up ), extracellular polymeric substances (EPS) production and solids retention time (SRT), focusing on their effects on granule formation and process performance. EGSB stability is governed by defined operational limits, with optimal performance at OLRs of 10–30 kg COD m −3 d −1 , VFAs below 500–1000 mg L −1 , and moderate V up (3–6 m h −1 ). Exceeding critical thresholds in VFA, V up , or influent solids (>5000 mg L −1 ) induces washout and granulation failure, while protein-rich EPS enhance the cohesion and shear resistance of granular biomass under high hydraulic and organic loads. Special attention is paid to microbial community dynamics, emphasizing how substrate characteristics, operational conditions, height-to-diameter ratio, and microbial kinetics jointly shape community shifts, syntrophic interactions, and overall process stability in EGSB reactors. Furthermore, the insights derived from these analyses are used to provide a more robust explanation of anaerobic granulation mechanisms, integrating conceptual models, key physicochemical drivers, and the role of quorum sensing (QS). Based on this integrated framework, this review identifies existing knowledge gaps and proposes future directions to support the development of robust and efficient EGSB systems for the sustainable treatment of complex industrial wastewaters.