The study explored slaughterhouse waste (SHW) as prime feedstock associated with and without supplement of an external slowly degradable lignocellulosic carbon source to overcome the synergistic co-inhibitions of ammonia and fatty acids. Long-term solid-state digestion (SSD) and liquid-state digestion (LSD) were investi-gated using a mixture of pork liver and fat. At 2.0 g volatile solids (VS) L-1 d-1 of organic loading rate (OLR), the two reactors of SSD experienced operational instability due to ammonia inhibition and volatile fatty acid (VFA) accumulation while LSD successfully produced 0.725 CH4 L CH4 g- 1VS during 197 d of working days under unfavorable condition with high total ammonia nitrogen (> 4.7 g/L) and VFAs concentration (> 1.9 g/L). The network analysis between complex microflora and operational parameters provided an insight for sustainable biogas production using SHW. Among all, hydrogenotrophic methanogens have shown better resistance than acetoclastic methanogens.