The present work focused on the comparative analysis of organic Rankine cycle (ORC) operated with nanoparticles. The effect of CuO and Al2O
3 nanoparticles synthesized with water and circulated within heat exchangers are examined. Thermal efficiency and levelized energy cost (LEC) of the nanofluid based ORC are evaluated simultaneously in the present work. The optimization problem of ORC is formed and solved using heat transfer search algorithm. Operating parameters of the nanofluid based ORC such as pinch point temperature difference of heat exchangers, evaporation pressure, the mass flow rate of refrigerant, and concentration of nanoparticles are investigated in the optimization study. Further, the effect of turbine ratio, heat source temperature, and mass flow rate of heat source fluid on CuO and Al
2O
3 based ORC is explored and discussed. It was observed that a total variation of 35.2% was obtained at the cost of 3.5% variation in LEC between extreme design points. The maximum thermal efficiency of 19.3% and 19.32% can be obtained with CuO and Al
2O
3 with 2.616 and 2.62 $/kWh, respectively. Comparative results reveal that CuO based ORC shows dominance in terms of economic performance over Al
2O
3 based ORC for any given value of the thermal efficiency.