The anaerobic treatment of pharmaceutical wastewater, characterized by high concentrations of antibiotics and sulfate, faces severe microbial competition and toxicity. Although two-phase anaerobic digestion (TPAD) offers a spatial decoupling strategy, its effectiveness is undermined by antibiotic-induced inhibition. To restore this decoupling paradigm, this study introduced a spatially differentiated conductive materials strategy, applying nanoscale zero-valent iron (nZVI) in the acidogenic phase (Ra) and sulfidated nZVI (S-nZVI) in the methanogenic phase (Rm). This approach synergistically optimized front-end detoxification and back-end methane production. In Ra, nZVI significantly promoted the degradation of sulfamethoxazole (78%) and the removal of sulfate (65%), which was associated with the enrichment of functional microbes such as the genus Desulfovibrio. During the Rm, S-nZVI significantly enhanced methane production by 47% to 2248 mL/d. This enhancement was achieved by establishing a stable ecological niche for methanogenic archaea such as Methanothrix, while simultaneously promoting extracellular electron transfer through the production of redox mediators such as humic acid and riboflavin. Furthermore, compared with the stage before S-nZVI addition, S-nZVI reduced the abundance of antibiotic resistance genes and mobile genetic elements in the Rm by 64% and 27%, respectively. This work demonstrates that integrating functionally differentiated conductive materials into a TPAD system can establish a robust bioprocess, achieving simultaneous pollutant removal, methane production, and risk control for recalcitrant wastewater.