In this study, a mathematical and numerical modeling of the photovoltaic (PV)-thermal solar system to power the multistage flashing chamber process is presented. The proposed model was established after the mass and energy conservation equations written for finite control volume were integrated with properties of the water and nanofluids. The nanofluids studied and presented herein are Ai2O3, CuO, Fe3O4, and SiO2. The multiple flashing chamber process was studied under various conditions, including different solar radiation levels, brine flows and concentrations, and nanofluid concentrations as well as flashing chamber temperatures and pressures. Solar radiation levels were taken as 500 w/m2, 750 w/m2, 1000 w/m2, and finally, 1200 w/m2. The nanofluid volumetric concentrations considered varied from 1% to 20%. There is clear evidence that the higher the solar radiation, the higher the flashed flow produced. The results also clearly show that irreversibility is reduced by using nanofluid Ai2O3 at higher concentrations of 10% to 20% compared to water as base fluid. The highest irreversibility was experienced when water was used as base fluid and the lowest irreversibility was associated with nanofluid SiO2. The irreversibility increase depends upon the type of nanofluid and its thermodynamic properties. Furthermore, the higher the concentration (e.g., from 10% to 20% of Ai2O3), the higher the availability at the last flashing chamber. However, the availability is progressively reduced at the last flashing chamber. Finally, the predicted results compare well with experimental data published in the literature.