Photovoltaic (PV) systems encounter substantial losses throughout their lifespan due to the different derating factors of PV modules. Those factors mainly vary according to the geographical location and PV panel characteristics. However, the available literature does not explicitly concentrate on the technical and economic impact of the derating factors within the PV system. Owing to that necessity, this study performs a comprehensive analysis of various PV loss parameters followed by a techno-economic assessment of derating factors using the average value on a grid-connected and optimally tilted PV system located in Hatiya, Bangladesh. Some criteria linked to the derating factors such as PV degradation and ambient temperature are further explored to analyze their impact on the aforementioned power system. Simulation results show that PV power generation would vary around 12% annually, subject to a 10% variation in the derating factor. Again, a 10% difference in the derating factor changes the net present cost (NPC) by around 3% to 4%. The system provides the best technical performance concerning annual PV production, power trade with the grid, and the renewable fraction at a higher value of the derating factor since it represents a lower impact of the loss parameters. Similarly, the financial performance in terms of the NPC, levelized cost of energy (LCOE), and grid power exchange cost is found to be lower when the derating factor value is higher.