In this present paper, a thermo-economic analysis is carried to study the performance and feasibility of using nanofluids as heating fluids in an integrated solar power generation plant (ISPGP). The integrated power generation plant consists of the solar field that is represented by parabolic trough solar collectors (PTSCs), a thermal energy storage system, and a power block. The effect of dispersing copper (Cu) and silver (Ag) nanoparticles into Therminol VP-1 and Syltherm 800 fluids is investigated. The effect of the nanofluids on the power output, energetic and exergetic efficiencies, and entropy generation of the PTSC is studied, in addition to their effect on the output performances and cost parameters of the ISPGP for 2 modes of operation. The first mode of operation assumes no storage, while the second mode of operation assumes a storage period of 7 hours. The most efficient nanofluids are selected to replace Therminol and Syltherm. Yearly, monthly, and daily analyses are carried to study the magnitude of improvement that is caused by the nanofluids on the performance of the PTSC and ISPGP. The simulation results show that the presence of the nanofluids decreased the pressure drop inside the PTSC and lowered the required pumping power. Moreover, it is established that 5% Cu/Therminol and 4% Ag/Therminol are the best replacements for Therminol for the first and second modes of operation, respectively; 5% Ag/Syltherm is the best replacement for Syltherm for both modes of operation. The monthly power output of the PTSC is increased by 11.1% and 11.7% when 5% Cu/Therminol and 4% Ag/Therminol are used, whereas an increase of 18.2% occurs when 5% Ag/Syltherm is used. The nanofluids increased the total power output of the ISPGP while decreasing the levelized cost of electricity (LEC). For instance, when comparing 5% Ag/Syltherm with Syltherm, the annual energy output increased from 121 to 125 GWh, while the LEC decreased from 5.86 to 5.70 c/kWh. In addition, it is proven that the ISPGP performs better when the thermal energy storage system is used. For example, when Therminol is used, the annual energy output of the ISPGP increased from 123 to 208 GWh and the LEC was lowered from 5.75 to 4.11 c/kWh.