Abstract Microalgal treatment can couple pharmaceutical attenuation with organic-matter and nutrient removal, but the operating windows for saline and freshwater species remain insufficiently defined. This laboratory study combined a central composite design, dual-detector confirmation of cortisone acetate (CA) removal, biomass mass balance, and artificial neural network (ANN) modelling and genetic algorithm (GA) optimisation to evaluate Tetraselmis chui (T. chui) and Scenedesmus obtusus (S.