<p>Upgrading the process water (PW) produced by hydrothermal carbonization (HTC) of organic waste before its treatment in anaerobic digestion (AD) could help increase the chemical oxygen demand (COD) degradation achieved and the methane production. To do so, large N- and O-containing aromatics, often formed through Maillard reactions and which are usually recalcitrants and/or inhibitors to AD, need to be removed or degraded. Different approaches were tested to upgrade PW, in order to improve their valorization in AD, including chemical, physical, and enzymatic treatments. The adaptation of the inoculum to the substrate was also compared to the upgrading treatment methods. Under conditions characterized by high inhibition, the enzymatic and UV treatments were the most effective methods tested, resulting in maximum methane production increases of 87% and 60%, respectively, compared to the control. The adaptation of the microbial communities was shown to increase the methane production rate, but led to an overall decrease of the methane yield. While it was possible to upgrade the PW for AD, the effect of the treatment methods was highly dependent on the inoculum used, as it was demonstrated that some inocula were more inhibited by the PW than others. The conversion of VFAs by SAO bacteria into CO₂ and H₂, and the subsequent methanation of these compounds by hydrogenotrophic methanogens, was identified as a key pathway for PW conversion. A very high abundance of acetoclastic methanogens (&gt; 80%) was also shown as a way to alleviate the inhibition effect and leads to a high methane production.</p>