In recent years, the development and use of polymeric nanocomposites in creating advanced materials has expanded exponentially. A substantial amount of research has been done in order to design polymeric nanocomposites in a safe and efficient manner. In the present study, the impact of processing parameters, such as, barrel temperature, and residence time on the mechanical and thermal properties of high density polyethylene (HDPE)-TiO2 nanocomposites were investigated. Additionally, scanning electron microscopy and X-ray diffraction spectroscopy were used to analyze the dispersion, location, and phase morphology of TiO2 on the HDPE matrix. Mechanical tests revealed that tensile strength of the fabricated HDPE-TiO2 nanocomposites ranged between 22.53 and 26.30 MPa, while the Young’s modulus showed a consistent increase as the barrel temperature increased from 150 °C to 300 °C. Moreover, the thermal stability decreased as the barrel temperature increased.