The Partial Or No Known Crystal Structure (PONKCS) method, an XRD analysis technique, is widely employed for phase quantification in cement-blended supplementary cementitious materials (SCMs). This study emphasized unsolved factors in applying this method to SCMs blends, including obtaining accurate SCM structure information, accounting for chemical composition variation, and identifying suitable C–S–H profiles. Ground granulated blast furnace slag was chosen as the representative SCM. Results show that four fundamental parameter (FP) type peaks were sufficient to index slag pseudo-structure without Pawley fitting. Slag weight fraction quantification was minimally impacted by slag pseudo-structures from slag with SiO2 content variations up to 3.03%. The C–S–H profile, with negligible clinker residue and a Lorentzian crystallite size of approximately 6.9 nm, was found suitable for PONKCS method application. Combining selective dissolution method with PONKCS method improved its accuracy. This study enhances improving quantification precision and extending the applications of PONKCS method in variable SCMs systems.