Heat pipe is a two phase heat transfer device with high effective thermal conductivity and transfer huge amount of heat with minimum temperature gradient in between evaporator and condenser section. This paper objective is to predict the thermal performance in terms of thermal resistance (R) and heat transfer coefficient (h) of screen mesh wick heat pipe with DI water-TiO2 as working fluid. The input process parameters of heat pipe such as heat load (Q), tilt angle (?) and concentration of nanofluid (?) were modeled and optimized by utilizing Response Surface Methodology (RSM) with MiniTab-17 software to attain minimum thermal resistance and maximum heat transfer coefficient. The minimum thermal resistance of 0.1764 0C/W and maximum heat transfer coefficient of 1411.52 W/m2 0C was obtained under the optimized conditions of 200 W heat load, 57.20 tilt angle and 0.159 vol. % concentration of nano-fluid.