This review summarizes current evidence on biomarkers for response to TIL therapy. TIL therapy has shown durable clinical responses in metastatic melanoma, with promising results in other malignancies. TILs are more effective than single antigen-targeted therapies due to their ability to traffic to the tumor site. The therapy involves resecting a tumor, culturing TILs in IL-2-enriched media, and expanding them before infusion. Lymphodepleting chemotherapy and IL-2 administration support TIL function. Tumor-related biomarkers include TMB, neoantigen load, and driver gene status. High TMB and neoantigen load correlate with better responses. However, low neoantigen load is a negative biomarker. Tumor immune infiltration and favorable transcriptomic signatures also correlate with clinical responses. Patient-related biomarkers include PS, LDH levels, and disease burden. Patients with PS ≥2 are underrepresented, and those with high LDH levels may still benefit from TIL therapy. Prior exposure to ICI and other therapies may influence response. Treatment-related biomarkers include TIL procurement, cell expansion, and patient conditioning. Short ex vivo culture times and high cell counts are strong predictors of response. TIL phenotype, including CD8:CD4 ratio, costimulatory molecules, and exhaustion markers, also influence efficacy. The review highlights the importance of identifying predictive biomarkers for optimal patient selection. While some biomarkers show promise, further research is needed to validate their predictive value and understand their role in TIL therapy. The complexity of TIL therapy, including toxicity and manufacturing challenges, limits its widespread use. However, ongoing research and clinical trials continue to explore ways to improve TIL therapy outcomes.This review summarizes current evidence on biomarkers for response to TIL therapy. TIL therapy has shown durable clinical responses in metastatic melanoma, with promising results in other malignancies. TILs are more effective than single antigen-targeted therapies due to their ability to traffic to the tumor site. The therapy involves resecting a tumor, culturing TILs in IL-2-enriched media, and expanding them before infusion. Lymphodepleting chemotherapy and IL-2 administration support TIL function. Tumor-related biomarkers include TMB, neoantigen load, and driver gene status. High TMB and neoantigen load correlate with better responses. However, low neoantigen load is a negative biomarker. Tumor immune infiltration and favorable transcriptomic signatures also correlate with clinical responses. Patient-related biomarkers include PS, LDH levels, and disease burden. Patients with PS ≥2 are underrepresented, and those with high LDH levels may still benefit from TIL therapy. Prior exposure to ICI and other therapies may influence response. Treatment-related biomarkers include TIL procurement, cell expansion, and patient conditioning. Short ex vivo culture times and high cell counts are strong predictors of response. TIL phenotype, including CD8:CD4 ratio, costimulatory molecules, and exhaustion markers, also influence efficacy. The review highlights the importance of identifying predictive biomarkers for optimal patient selection. While some biomarkers show promise, further research is needed to validate their predictive value and understand their role in TIL therapy. The complexity of TIL therapy, including toxicity and manufacturing challenges, limits its widespread use. However, ongoing research and clinical trials continue to explore ways to improve TIL therapy outcomes.