This study investigates the scalability of nanopulsed plasma bubble technology for water remediation, transitioning from lab to pilot scale. The pilot-scale plasma bubble reactor was optimized to degrade toxic organic pollutants, including dyes (methylene blue, MB), antibiotics (sulfamethoxazole, SMX), and pharmaceuticals (valsartan, VAL). High degradation efficiencies were achieved: >99% for MB after 10 min, >99% for SMX after 20 min, and >98% for VAL after 40 min. The reactor produced high concentrations of short-lived hydroxyl radicals (·OH, ~25 mg/L under O2), with minimal long-lived species (O3, H2O2, NO3-/NO2-), maintaining stable pH (~7). Energy efficiency was superior at the pilot scale, with electrical energy per order (EEO) values of 0.18 kWh/m3 for MB, 0.42 kWh/m3 for SMX, and 0.88 kWh/m3 for VAL, 2-3 orders of magnitude lower than other advanced oxidation processes (AOPs). The system’s performance was consistent across tap and ultrapure water, demonstrating its applicability in real-world conditions. These findings highlight the potential of nanopulsed plasma bubbles for rapid, effective, and energy-efficient water remediation at larger scales.