Endometrial decidualization resistance (DR) is implicated in various gynecological and obstetric conditions. Here, using a multi-omic strategy, we unraveled the cellular and molecular characteristics of DR in patients who have suffered severe preeclampsia (sPE). Morphological analysis unveiled significant glandular anatomical abnormalities, confirmed histologically and quantified by the digitization of hematoxylin and eosin-stained tissue sections. Single-cell RNA sequencing (scRNA-seq) of endometrial samples from patients with sPE (n = 11) and controls (n = 12) revealed sPE-associated shifts in cell composition, manifesting as a stromal mosaic state characterized by proliferative stromal cells (MMP11 and SFRP4) alongside IGFBP1