This study compared the effectiveness of the Sequencing Batch Biofilter Granular Reactor (SBBGR) plant with and without the integration of ozone (BIO-CHEM process) in the remediation of medium-aged landfill leachate. Special attention is given to the removal of per- and polyfluoroalkyl substances (PFAS) as a group of bioaccumulative and persistent pollutants. The findings highlight the high SBBGR performance under biological process only for key wastewater contaminants, with 82% for chemical oxygen demand (COD), 86% for total nitrogen, and 98% for ammonia. Moderate removal was observed for total (TSS) and volatile (VSS) suspended solids (41% and 44%, respectively), while phosphorus and colour removal remained limited. Remarkably, the SBBGR process achieved complete removal of long-chain PFAS, while its performance declined for shorter-chain PFAS. BIO-CHEM process significantly improved COD (87.7%), TSS (84.6%), VSS (86.7%), and colour (92–96%) removal. Conversely, ozonation led to an unexpected increase in the concentrations of several PFAS in the effluent, suggesting ozone-induced desorption from the biomass. SBBGR treatment was characterised by a low specific sludge production (SSP) value, i.e., 5–6 times less than that of conventional biological processes. SSP was further reduced during the application of the BIO-CHEM process. A key finding of this study is a critical challenge for PFAS removal in this combined treatment approach, different from other ozone-based methods.