A long-term evaluation of hythane generation from unsaturated polyester resin wastewater contaminated by 1,4-dioxane and heavy metals was investigated in a continuous up-flow anaerobic self-separation gases (UASG) reactor inoculated with mixed culture. The reactor was operated at constant hydraulic retention time (HRT) of 96 h and different organic loading rates (OLRs) of 0.31 +/- 0.04, 0.71 +/- 0.08 and 1.07 +/- 0.06 gCOD/L/d. Available data showed that volumetric hythane production rate was substantially increased from 0.093 +/- 0.021 to 0.245 +/- 0.016 L/L/d at increasing OLR from 0.31 +/- 0.04 to 0.71 +/- 0.08 gCOD/L/d. However, at OLR exceeding 1.07 +/- 0.06 gCOD/L/d, it was dropped to 0.114 +/- 0.016 L/L/d. The reactor achieved 1,4-dioxane removal efficiencies of 51.8 +/- 2.8, 35.9 +/- 1.6 and 26.3 +/- 1.6% at initial 1,4-dioxane concentrations of 1.14 +/- 0.28, 1.97 +/- 0.41 and 4.21 +/- 0.30 mg/L, respectively. Moreover, the effect and potential removal of the contaminated by heavy metals (i.e., Cu2+, Mn2+, Cr3+, Fe3+ and Ni2+) were highlighted. Kinetic modelling and microbial community dynamics were studied, according to each OLR, to carefully describe the UASG performance. The economic analysis showed a stable operation for the anaerobic digestion of unsaturated polyester resin wastewater using UASG, and the maximum net profit was achieved at OLR of 0.71 +/- 0.08 gCOD/L/d.