Abstract: Abstract: Objective: To investigate the critical role of disulfidptosis-elevated cancer-associated fibroblasts (CAFs) in promoting tumor growth and modulating the immune microenvironment. Methods: Multi-omics analyses were conducted using TCGA, GEO, and single-cell RNA sequencing data. Techniques included bulk RNA-seq, single-cell clustering, CellChat interaction network analysis, and spatial transcriptomics to characterize the expression profiles of disulfidptosis-related genes (DRGs) and the functional heterogeneity of CAF subpopulations. Quantitative PCR was performed to validate DRG and SPP1 expression under glucose starvation conditions. Results: The key disulfidptosis gene SLC7A11 was highly expressed in ovarian cancer tissues and positively correlated with clinical stage, tumor size, and resistance to immunotherapy. Single-cell analysis showed DRG enrichment in CAF1 and CAF5 subtypes, which promoted epithelial–mesenchymal transition (EMT) and immune suppression via the SPP1–CD44 axis. Spatial transcriptomics revealed specific accumulation of SPP1 at the CAF–tumor cell interface, forming strong interaction networks with ITGAV, ITGB1, and CD44. Glucose deprivation significantly downregulated the expression of DRGs and SPP1. Conclusion: Elevated disulfidptosis in CAFs contributes to immune suppression and facilitates tumor progression by orchestrating cell–cell interactions within the tumor microenvironment. These findings provide new insights into CAF-mediated immune regulation and suggest disulfidptosis as a potential therapeutic target in cancer.