Background: Cervical cancer (CC) remains a major public health challenge in Brazil, characterized by high incidence and pronounced regional disparities in clinical outcomes. To address these national inequalities, this study employs multi-omic profiling as a key approach to characterize the molecular landscape of CC. Objectives and Methods: This study integrated whole-genome and transcriptomic data to explore molecular alterations associated with CC in a Brazilian cohort. Differentially expressed genes (DEGs) were analyzed in recurrent versus non-recurrent tumors, as well as in tumors and cervical precursor lesions, providing insights into the biological processes associated with disease progression. Whole-genome (WGS) and transcriptome (RNA-seq) sequencing were conducted on cervical cancer and precursor lesion samples. HPV genotyping was performed with Multiplex Polymerase Chain Reaction (PCR) followed by DNA-Flow Chip (Reverse Hybridization). Sequencing libraries were prepared with Illumina kits and sequenced on the NovaSeq X Plus platform. WGS data were processed according to Broad Institute best practices via nfcore/sarek pipelines. For RNA-seq, the bioinformatics workflow included quality control (FastQC), read alignment (STAR), gene expression quantification (Salmon), differential expression analysis (DESeq2), and functional enrichment analysis (fgsea). Results: The cohort comprised 73 squamous cell carcinomas (SCC; 23 recurrent, 50 non-recurrent), 23 adenocarcinomas (AC; 15 recurrent, 8 non-recurrent), and 45 high-grade precursor lesions (HSIL/CIN3). Comparative transcriptomic analysis between CIN3 and SCC identified a consistent downregulation of genes involved in chromatin organization and genomic maintenance, including H2AC18, H2AZ1, and RMI1, suggesting molecular alterations associated with malignant progression. Analysis of tumor recurrence revealed histology-specific transcriptomic signatures. In recurrent SCC, differential expression was observed in genes related to proliferative signaling and cell differentiation, with upregulation of RASGEF1C and selected long non-coding RNAs, alongside reduced expression of genes associated with apoptosis and cell adhesion. In contrast, recurrent AC displayed a distinct expression profile enriched for genes involved in developmental signaling and immune-related pathways, including upregulation of SOX10 and MRC1 and downregulation of immune- and tumor suppressor–related genes. These findings highlight divergent molecular patterns associated with recurrence across cervical cancer histological subtypes. Conclusions and Implications: Integrated genomic and transcriptomic analyses of this Brazilian cervical cancer cohort identified distinct molecular patterns associated with malignant progression and tumor recurrence. Alterations related to chromatin organization characterized the transition from high-grade precursor lesions to invasive disease, while recurrence was associated with histology-specific transcriptomic profiles in squamous cell carcinoma and adenocarcinoma. Together, these findings refine the molecular stratification of cervical cancer in Brazil and provide candidate pathways for future studies on risk assessment and therapeutic response.