The success of plastics heavily relies on fast melt processing methods used for large-scale industrial manufacturing, including injection molding. The hierarchical structure of the solid polymer depends on material selection combined with processing conditions, making mechanical properties of the injection molded part difficult to predict. Here we show how scanning small- and wide-angle X-ray scattering, birefringence microscopy, and polarized light optical microscopy can be combined with injection molding simulations to shed light on the correlation between the polymer morphology of high-density polyethylene and processing conditions. The scattering data revealed that the complex layered structure highly depends on the pressure during the holding phase of injection molding. Furthermore, we identified specific work of flow as a main parameter to capture the changes in morphology induced by varying the process settings. Overall, a good agreement was found between experimental data and the computational simulations, suggesting that computational simulations can be further used to predict the multiphase morphology of injection molded parts.