Supersymmetric models are characterized by a strong diversity of experimental signatures. Since general-purpose searches have not yet given any clear indication of new physics, dedicated methodologies and tools have been developed to target the regions of the parameter space where the analysis is most challenging and SUSY might still lie undetected. This contribution will describe relevant examples among searches performed by the CMS Collaboration using the full dataset of proton-proton collisions collected during the Run 2 of the LHC at a center-of-mass energy of 13 TeV.