ABSTRACT Fusobacterium nucleatum ( F. nucleatum ), a prevalent anaerobe primarily colonizing the oral cavity, functions as both a commensal biofilm architect and an opportunistic pathogen. Increasing evidence implicates it in a wide spectrum of inflammatory diseases and malignancies. This review synthesizes current knowledge with emphasis on subspecies‐specific functional distinctions and pathological relevance. Beyond its established roles in oral inflammation, atherosclerosis, and adverse pregnancy outcomes, F. nucleatum is emerging as a key oncomicrobe, particularly in colorectal cancer. It can translocate from the oral niche to extra‐oral sites, where it fuels chronic inflammation and promotes tumor initiation, progression, metastasis, and therapy resistance. Pathogenic mechanisms include host transmission pathways, adhesion and colonization strategies, induction of inflammatory cascades, enhancement of cellular proliferation and metastatic potential, immune modulation, and contribution to therapeutic resistance. We further explore its dynamic interactions with host cells and microbial communities, highlighting how microbial synergy and antagonism shape disease outcomes. Current and emerging therapeutic and preventive strategies targeting F. nucleatum are systematically evaluated. A nuanced understanding of the context‐dependent pathogenicity of F. nucleatum and its ecological interactions is critical for advancing the development of robust diagnostic biomarkers and precision therapeutics aimed at mitigating its disease burden.