High polymer-modified binders (HiPMBs) have recently been introduced in the Gulf region, where pavement structures are commonly subjected to severe climate conditions and heavy traffic loads because there is no enforcement of weight limits. Local agencies are currently modifying quality assurance/quality control (QA/QC) policies to accommodate such technology. In this study, HiPMBs produced by different refineries were subjected to physicochemical and thermal characterizations to investigate the compositional variability of industrial HiPMBs. Their thermal and stress susceptivity was then assessed through multiple stress creep recovery (MSCR) tests. The validation of the MSCR-based hierarchy was performed by assessing nine hot mix asphalts (HMAs) through repeated load permanent deformation tests and performing mechanistic-based structural analysis. Results showed that styrene-butadiene-styrene (SBS) is not the only modifier added to the bitumen, as commonly done in laboratory settings. These undisclosed modifiers disrupt the correlation between MSCR results and SBS concentration typically observed in laboratory-prepared HiPMBs, highlighting the importance of investigating plant-produced binders. Moreover, higher temperatures and stress levels returned different MSCR performance hierarchies among binders, questioning the effectiveness of the current MSCR test protocol for HiPMBs. Additionally, findings confirmed that the current MSCR testing protocol does not correctly assess the bitumen response in HMAs. A higher MSCR stress level shall be prescribed in the local QA/QC specifications to ensure the correct selection of HiPMBs in the region. This study can be used as a framework for other countries actively engaged in the implementation of HiPMBs and novel bituminous materials.