This study provides an integrated assessment of UV/H2O2 treatment of different real wastewater matrices: two urban wastewater treatment plants (WWTPs) secondary effluents, greywater, hospital, and pharmaceutical industrial effluents. It considers micropollutant removal (up to 30 pharmaceuticals and 13 transformation products at environmental concentrations), energy efficiency and effluent toxicity. The complexity of the wastewater matrix negatively affected the UV fluence in the photo-reactor, scavenged hydroxyl radicals and hindered a proper H2O2 utilization thus reducing the treatment efficiency. At the optimal treatment conditions, overall pharmaceuticals removal was the highest for urban WWTPs effluents (69%–86%), followed by greywater (59%), hospital (36%) and industrial (17%) effluents. The ecotoxicity of the treated samples was reduced around one toxicity unit after the UV/H2O2 treatment in all cases except in industrial wastewater. The average observed removal in urban wastewater effluents and greywater for photo-susceptible, moderately photo-susceptible, and most photo-resistant compounds was 93%, 73% and 46% including outliers, respectively. The calculated electrical energy per order (EEO) values were 0.9–1.5 kWh/(m3·order) for urban WWTP effluents and greywater while for hospital and industrial effluents was much higher (7.3–9.1 kWh/(m3·order)).