•Comparative study of water-cooled cooler block arrangements led to optimized PVT-III layout using Response Surface Methodology (RSM).•Introduction of 0.3 wt% TiO2/nanofluid, notably enhancing electrical efficiency in PVT systems.•Positive correlation identified between rising nanofluid concentration and improved system performance.•Peak electrical efficiencies were attained under elevated solar irradiance and flow rates. The current study presents a partitioned rectangular-shaped heat sink for improving the PVT system performance. The experiment was examined under various experimental parameters. Five cooler block types with different dimensions were arranged to share the same total contact area with the panel back surface. These cooler blocks were placed in different arrangements, namely (PVT-I, PVT-II, PVT-III, PVT-IV, PVT-V), and studied comparatively using water. The dimensions and numbers of each cooler block arrangement were altered, while maintaining the same surface area in contact with the photovoltaic panel. Through the response surface methodology (RSM) optimization, the optimal arrangement with the best performance was determined, and then TiO2/nanofluid was applied to that arrangement with different volumetric concentrations. Using water, the highest electrical and thermal efficiencies were obtained by case PVT-III with values of 19.39 % and 63.72 %, respectively. This was followed by PVT-II, PVT-V, PVT-I, and PVT-IV in that order for electrical efficiency; and at the same time by PVT-II, PVT-I, PVT-IV, and PVT-V in that order for thermal efficiency. The RSM method recommended the optimal arrangement case as case PVT-III. By using nanofluid in that case arrangement, the highest electrical efficiency value was recorded upon using 0.3 wt% and operating the system at 1.5 L/m and 900 W/m2. Regarding the thermal efficiency results, in that case, the highest and lowest values were recorded upon using 0.3 wt% and 0.1 wt%, respectively, with values of 72.49 % and 31.19 %. Increasing the volumetric concentrations positively reflected on the system's performance, resulting in high efficiencies being achieved. In addition, the highest electrical efficiencies were obtained at high levels of solar irradiance and flow rates.