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Background: Nedylation and tumours are closely linked. The role of nedylation in bladder cancer (BCa) has rarely been reported and this study aims to explore its potential impact on the pathogenesis and progression of BCa., Methods: Leveraging gene expression data from the TCGA database, this research employs the limma software package and WGCNA for gene module identification and analysis. Subsequent steps include the construction of a PPI network, the conduct of LASSO and univariate Cox regression analyses, and utilizing GSEA and single-cell sequencing to examine the influence of hub genes in bladder cancer-related biological pathways., Results: The investigation revealed 11,361 genes with significant differential expression between normal and tumour tissues, and identified 1,500 hub genes through analysis. LASSO regression identified eight critical genes. Univariate Cox regression analysis revealed that COMMD9, GPS1, PSMB5, VHL, and WDR5 are independent prognostic factors for BCa. GSEA and single-cell sequencing highlight the potential of these genes to modulate immune responses and interactions between tumour and immune cells. Meanwhile, GSEA demonstrated that GPS1 can activate the NF-κB signalling pathway, leading to an increase in influenza virus polymerase activity., Conclusion: This study identifies COMMD9, GPS1, PSMB5, VHL, and WDR5 as significant prognostic markers in BCa, thereby underscoring their roles in immune regulation and tumour-immune cell dynamics., Competing Interests: None., (AJCEU Copyright © 2024.)