Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota—such as probiotics, dietary modifications, and fecal microbiota transplantation—offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.