This paper aims to assess the impact of different key factors on the optimized design and performance of grid connected photovoltaic (PV) power plants, as such key factors can lead to re-design the PV plant and affect its optimum performance. The impact on the optimized design and performance of the PV plant is achieved by considering each factor individually. A comprehensive analysis is conducted on nine factors such as; three objectives are predefined, five recent optimization approaches, three different locations around the world, changes in solar irradiance, ambient temperature, and wind speed levels, variation in the available area, PV module type and inverters size. The performance of the PV plant is evaluated for each factor based on five performance parameters such as; energy yield, sizing ratio, performance ratio, ground cover ratio, and energy losses. The results show that the geographic location, a change in meteorological conditions levels, and an increase or decrease in the available area require the redesign of the PV plant. A change in inverter size and PV module type has a significant impact on the configuration of the PV plant leading to an increase in the cost of energy. The predefined objectives and proposed optimization methods can affect the PV plant design by producing completely different structures. Furthermore, most PV plant performance parameters are significantly changed due to the variation of these factors. The results also show the environmental benefit of the PV plant and the great potential to avoid green-house gas emissions from the atmosphere.