Fusobacterium nucleatum is an opportunistic bacterial pathogen and oncogenic microbe. Using host sequencing data to systematically investigate Fusobacterium-host interactions in colorectal cancers (CRCs), we developed and orthogonally validated a multi-omics PAThogen CHaracterisation tool (PATCH) enabling gene-level annotations. In 1,020 CRC transcriptomes and 86 genomes from The Cancer Genome Atlas (TCGA), 9 Fusobacterium species were detected to gene-level resolution identifying carcinogenic virulence factors. PATCH uncovered the integration of Fusobacterium’s DNA into the host genome, specifically in non-coding regions and near Short Interspersed Elements. CRCs with integrated-Fusobacterium DNA revealed perturbations in host DNA damage response mechanisms, including deficiencies in chromosome segregation, increased microsatellite instability, elevated cytosolic DNA/RNA sensing signalling, and mutations in genes involved in oncogenic-related pathways. Fusobacterium-positive CRCs exhibited global LINE-1 hypomethylation, suggesting a potential integration path into non-coding regions. Our analytical approaches have delineated Fusobacterium’s multimodal contribution to disrupting genomic stability in CRC, which could facilitate tailored treatment options.