Pre-concentrated domestic wastewater (PDWW) rich in organic matters can be a suitable substrate for anaerobic digestion (AD) towards holistic resource and bioenergy recovery. Micron zero-valent iron (ZVI) was applied in designed batch experiments during anaerobic treatment of PDWW to verify its roles in performance enhancement and associated mechanisms. In the selected range of food to microorganism (F/M) ratio, 0.5 gCOD/gMLVSS was most appropriate as biomethane production potential (BMP) of 0.275 L CH/gCOD was obtained. The optimal ZVI dosage at fixed F/M of 0.5 was 6 g/L, further enhancing the BMP by 15.2%. Furthermore, ZVI improved the hydrolysis process (producing more soluble organics) and regulated acidification process (affecting volatile fatty acids distribution). No obvious impact on acetoclastic and hydrogenotrophic methanogenesis processes was noted with ZVI addition. ZVI based AD of the PDWW is promising for promoting the practical application of advanced domestic wastewater treatment strategy (pre-concentration plus anaerobic digestion).