Tetraselmis suecica was cultivated in a semi-continuously operated tubular photobioreactor fed on aquaculture wastewater (AW) testing two hydraulic retention times (HRT): 10 and 7 days (RUN_1 and RUN_2, respectively). The integrated mechanistic model BIO_ALGAE was validated with experimental data in order to simulate the biomass production and nutrient uptake of T. suecica. Moreover, AW was used as substitute synthetic cultivation medium to test the production of lipids, proteins, and carbohydrates in the microalgal biomass. Preliminary photo-respirometric tests were carried out on the AW suspension containing microalgae and bacteria. Dissolved Inorganic Nitrogen (DIN) and Dissolved Inorganic Phosphorus (DIP) were analyzed for the two RUNs, and no significant difference was highlighted (p > 0.05). On the contrary, the productivity of the Total suspended solids (TSS) was significantly higher (p < 0.05) for RUN_1 (900 mg TSS/L) than for RUN_2 (550 mg TSS/L). The analysis of the biochemical composition of biomass has demonstrated a higher content of proteins than of lipids and carbohydrates for the two RUNs. BIO_ALGAE model was validated by comparing simulated results to experimental data. The model was able to reproduce the pattern of these experimental data quite well, for both nutrient uptake and biomass production. The simulated curve follows the same pattern as the experimental data for both RUNs. The wavelike trend indicates the good accuracy of the simulated curves to reproduce the microalgae growth and nutrient uptake that occurring during daytime and at night. With this study, BIO_ALGAE Model was demonstrated to be useful to simulate bioremediation and microalgae production in aquaculture wastewater in a semi-continuous system with different environmental factors. The photo-respirometric outputs were compared with the process rates affecting dissolved oxygen dynamics computed by the mathematical model.