Low carbon/nitrogen (C/N) FW usually leads to the suboptimal anaerobic digestion (AD) process due to the imbalance of nutrients for microorganisms. Inoculum to substrate ratios (ISRs) can regulate the pathways of AD process but whether it can alleviate the insufficient nutrient availability remain an enigma. In this study, the Macau household food waste (HFW) is characterized by a low C/N ratio ranging between 6–19 (i.e. spring, 6; summer, 11; autumn, 19; winter, 11; annual mean, 11). As a representative, to quick-start the anaerobic digestion (AD) and maximize the methane production of the low C/N ratio HFW, different inoculum-to-substrate ratios (ISRs, 10/3; 2/1; 1/1 and 1/2) were examined in biochemical methane potential tests coupled with methanogenic pathway analyses. The maximum methane production of 0.4 m3/kg VS at ISR of 10/3 was achieved with a C/N ratio of 11. Increasing ISRs from 1/2 to 10/3 facilitated the methane production by not only predominating with acetoclastic methanogenesis (e.g. Methanosarcinales), but also strengthened the microbial metabolism in the hydrolysis of carbohydrates and proteins (e.g. ~60% reduction of relevant genus Aminobacterium). Lower ISRs (<1), whereas hydrogenotrophic methanogenic (e.g. Methanolinea) and syntrophic bacteria (e.g. Mesotoga and Syntrophomonas) dominated, followed the opposite pattern. Results of the present study provide fundamental information for the AD of FW with a low C/N ratio.