Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of renal cancer, accounting for approximately 75% of all kidney malignancies in adults. Despite advances in diagnosis and therapy, the molecular mechanisms underlying ccRCC progression remain incompletely understood. MicroRNAs (miRNAs), as post-transcriptional regulators of gene expression, play critical roles in cancer initiation, progression, and metastasis. This study aimed to identify key dysregulated miRNAs and their target genes involved in ccRCC pathogenesis using an integrative in-silico bioinformatics approach. Three Gene Expression Omnibus (GEO) datasets (GSE116251, GSE95384, and GSE6357) were analyzed through the GEO2R tool to identify differentially expressed genes (DEGs) and miRNAs (DEMs) using |logFC| > 1 and adjusted p-value < 0.05 as thresholds. Overlapping miRNAs were determined using the Venny tool, and their corresponding target mRNAs were predicted through TargetScan. Functional annotation and pathway enrichment of DEGs were performed using the DAVID database, while protein–protein interaction (PPI) networks were constructed through STRING. The miRIAD and OncomiR databases were employed to elucidate miRNA–gene interactions, and the OncoLnc database was utilized for survival analysis. Our analysis revealed several dysregulated miRNAs, including miR-155-5p, miR-210-3p, and miR-21-5p, along with key tumor-related genes such as VHL, PBRM1, SETD2, TP53, and PTEN, which significantly influence ccRCC prognosis. Functional enrichment analysis demonstrated that these genes are involved in critical oncogenic pathways, including the cell cycle, p53 signaling, and PI3K–Akt pathways. In conclusion, this study provides a comprehensive bioinformatic framework that highlights novel miRNA–gene interactions potentially involved in ccRCC progression. The identified molecules may serve as valuable biomarkers for diagnosis, prognosis, and targeted therapy in renal cancer, supporting further experimental validation and clinical investigation.