The targeted synthesis of crystalline microporous silicoaluminophosphate (SAPO) molecular sieves (MSs) with desired topologies is challenging. Conventionally, the trial-and-error approach assisted by computational methods is widely utilized for this exploration. The identification of predicted organic structure-directing agents (OSDAs) by this method is usually based on a neutral aluminophosphate or pure silica framework as the initial structural model, ignoring the host–guest interaction. To some extent, this may affect the prediction result. Herein, we present a novel approach called RSS (Refining, Summarizing, and Searching), which is used for identifying appropriate OSDAs for synthesizing specific SAPO MSs. The RSS approach is mainly based on understanding the structural roles of the alkyl groups of OSDAs and the host–guest interaction elucidated from refinement analysis against experimental diffraction data. By adopting the RSS approach, the OSDAs of a small pore SAPO MS DNL-6 (RHO topology) have been extended from two types reported by us to fourteen additional commercialized ones. DNL-6 has shown promising CO₂/N₂ gas separation and the unique intermediate heptamethylbenezenium cations have been identified in DNL-6 during the methional-to-olefin (MTO) reaction in our previous work. The universality of this approach manifests the targeted synthesis of another SAPO MS SAPO-42 (LTA topology) by employing cheap commercialized OSDAs. Before our work, this material could only be synthesized using complex and expensive OSDAs in a toxic F⁻ medium.