Antimicrobial resistance (AMR) poses a critical global public health challenge requiring comprehensive intervention strategies, including robust antibiotic stewardship programs. The European Commission’s 2017 One Health Action Plan against AMR established guidelines based on WHO’s AWaRe classification system, which categorizes antibiotics into Access, Watch, and Reserve groups to promote prudent use. However, the proliferation of substandard and falsified (SF) medical products increasingly undermines these stewardship efforts, with European regulatory agencies, including Belgium’s Federal Agency for Medicines and Health Products (FAMHP), reporting rising seizures of SF antibiotics. : To assess the pharmaceutical quality of confiscated antibiotic samples and evaluate their potential contribution to AMR development. We conducted comprehensive pharmaceutical quality control testing on 40 SF antibiotic samples seized by the FAMHP between early 2024 and late 2025. The analysis revealed significant deficiencies: 35% of samples contained antibiotics listed on international watch lists, while nearly 43% failed quality control testing. Dissolution defects represented the predominant failure mode, accounting for 29% of all samples tested. These defects can severely compromise drug bioavailability, clinical efficiency, and expose bacterial populations to sub-lethal concentrations of active pharmaceutical ingredients-a recognized driver of resistance development. Many seized samples appeared to be unregistered/unlicensed medicines that, while prohibited in the EU, may circulate legally elsewhere. This transnational dimension highlights how substandard products threaten global AMR control initiatives beyond individual patient safety. These findings underscore the urgent need to raise more awareness within the EU and for enhanced pharmaceutical quality assurance systems and much more international regulatory cooperation, particularly in low- and middle-income countries where such products circulate more readily.