This review examines the predictive biomarkers for monitoring the therapeutic response to anti-TNF therapy in patients with inflammatory bowel disease (IBD). Anti-TNF therapies, such as Infliximab and Adalimumab, have revolutionized the treatment of IBD by achieving clinical and endoscopic remission, promoting mucosal healing, and reducing the need for surgery. However, not all patients respond positively to these treatments, and some may experience a loss of responsiveness over time. The review explores various predictive biomarkers, including genetic, fecal, immune, protein, microbial, and anti-drug antibody markers, to provide a comprehensive understanding of their clinical utilities and limitations. Genetic markers, such as polymorphisms in genes like FCGR3A, TLR4, TNFRSF1A, IFNG, IL6, and IL1B, have been linked to treatment response. Fecal markers like calprotectin and lactoferrin show mixed results in predicting response. Immune markers, including cytokines and chemokines, can indicate treatment efficacy. Protein markers, such as ANG1, ANG2, CRP, and MMPs, also hold promise. Microbial markers, particularly those related to gut microbiome diversity and composition, are increasingly recognized as important. Anti-drug antibodies, which can lead to immunogenicity and treatment failure, are another critical factor. The review highlights the need for further validation studies to integrate these biomarkers into clinical practice for personalized treatment approaches.This review examines the predictive biomarkers for monitoring the therapeutic response to anti-TNF therapy in patients with inflammatory bowel disease (IBD). Anti-TNF therapies, such as Infliximab and Adalimumab, have revolutionized the treatment of IBD by achieving clinical and endoscopic remission, promoting mucosal healing, and reducing the need for surgery. However, not all patients respond positively to these treatments, and some may experience a loss of responsiveness over time. The review explores various predictive biomarkers, including genetic, fecal, immune, protein, microbial, and anti-drug antibody markers, to provide a comprehensive understanding of their clinical utilities and limitations. Genetic markers, such as polymorphisms in genes like FCGR3A, TLR4, TNFRSF1A, IFNG, IL6, and IL1B, have been linked to treatment response. Fecal markers like calprotectin and lactoferrin show mixed results in predicting response. Immune markers, including cytokines and chemokines, can indicate treatment efficacy. Protein markers, such as ANG1, ANG2, CRP, and MMPs, also hold promise. Microbial markers, particularly those related to gut microbiome diversity and composition, are increasingly recognized as important. Anti-drug antibodies, which can lead to immunogenicity and treatment failure, are another critical factor. The review highlights the need for further validation studies to integrate these biomarkers into clinical practice for personalized treatment approaches.