Contaminants of emerging concern (CEC) pose significant challenges to environmental and human health. The development of the wastewater reuse sector, coupled with progressively stringent regulations, needs innovative systems that integrate advanced treatment processes with in-situ and real-time monitoring of CEC. This study investigates the use of a tryptophan-like fluorescence sensor for real-time and online monitoring of CEC within a pilot plant employing O3-based advanced oxidation processes (AOPs). Two tertiary wastewater effluents (WW-1 and WW-2) were tested, placing the pilot system downstream of two different wastewater treatment plants (WWTPs). Priority substances and micropollutants detected in the investigated water matrixes such as pharmaceuticals, per- and polyfluoroalkyl substances (PFAS) were selected as targeted compounds in this study. Fluorescence degradation was detected in real-time by the sensor, showing a high capability to detect fast changes in water quality induced by oxidation. Furthermore, the real-time fluorescence showed better sensitivity than lab-scale fluorescence in detecting the fast action of hydroxyl radicals (·OH) during the O3/H2O2 process, highlighting the importance of online monitoring. Selected CEC were degraded by AOPs with different percentages of removal efficiency (RE) (0%<RE<100% in WW-1 and 15%<RE<90% in WW-2) depending on oxidant doses and the reactivity of compounds with O3 and ·OH. Fluorescence data by online sensor enabled accurate prediction of the removal of a wide spectrum of CEC during O3 and O3/H2O2 processes (R2≥0.93). Furthermore, real-time fluorescence data were successfully used to predict observed pseudo-first-order rate constants of CEC with O3 or O3/H2O2. Obtained results suggest that real-time fluorescence monitoring is an excellent tool to control CEC removal during O3-based AOPs and monitor the transferred ozone in wastewater (R2≥0.94), contributing to the optimization of reagent dose, energy and costs.