Hybrid PV/T (Photovoltaic/thermal) systems are a robust alternative to the limitations of PV panels and thermal collectors in energy production. Improving their performance is therefore necessary. This article presents a new configuration of hybrid photovoltaic and thermal (PV/T) air/water-CuO/MgO/TiO₂ collector which is optimized by seeking a better combination of design parameters which maximize the exergy performance. An energy and exergy analysis of the system is carried out and a multi-objective optimization with the genetic algorithm is developed using Matlab. These to determine the values of these nine (9) design parameters such as collector tilt angle, collector area, center to center distance between tubes, inside and outside diameter of tubes and thicknesses of the cells, of the glass layer, of the insulation, of the absorber. The other parameters are taken constant and a set of optimal solutions are sought for 1000 generations. The comparison of the different numerical results from this article with the design parameters from previous work shows good agreement. It is observed that the total exergy efficiency is maximum between the values of 23.41–36.6% and the majority of the design parameters studied in general are minimum. The discussions deduced that the minimization of the components of the bi-fluid PV/T hybrid collector could reduce the losses inside the latter by favoring the cooling as well as the displacement of the heat at the back of the PV cell. This work shows that the mixture of water and ternary nanoparticles with a flow rate of 0.00575 kg/s cooled more than air at 0.008 kg/s, but the system performed better when the two fluids operated simultaneously at 0.0035 kg/s. Due to the requirement of optimal efficiency and minimum costs, the hybridization of nanoparticles presents better thermo-economic performances.