This comprehensive review aims to summarize the current evidence on the potential impact of various factors on the response to adoptive cell therapy with tumor-infiltrating lymphocytes (TIL). The review covers tumor-related factors (mutational burden, neoantigen load, immune infiltration, oncogenic driver genes, and epigenetic modifications), patient characteristics (disease burden, baseline cytokines, lactate dehydrogenase levels, HLA haplotype, and prior exposure to immune checkpoint inhibitors), phenotypic features of transferred T cells (total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and target antigenic scope), and other treatment-related factors (lymphodepleting chemotherapy and postinfusion administration of interleukin-2). Key findings include: - High tumor mutational burden (TMB) and neoantigen load are strong predictors of response, even after progression on immune checkpoint inhibitors. - Baseline lactate dehydrogenase (LDH) levels and disease burden are associated with poorer outcomes. - Prior systemic therapies, particularly anti-PD-1 antibodies, do not significantly impact response likelihood. - Baseline serum cytokines and circulating factors, such as IL-9, may influence response. - Short pre-rapid expansion protocol (REP) culture times and high absolute cell counts are strong predictors of response. - TIL antitumor reactivity and phenotype-related parameters, such as CD8:CD4 ratio and exhaustion marker expression, are also important. - The interaction between TIL and the host immune microenvironment is complex and influenced by various factors. The review highlights the need for further research to optimize patient selection and improve the efficacy of TIL therapy.This comprehensive review aims to summarize the current evidence on the potential impact of various factors on the response to adoptive cell therapy with tumor-infiltrating lymphocytes (TIL). The review covers tumor-related factors (mutational burden, neoantigen load, immune infiltration, oncogenic driver genes, and epigenetic modifications), patient characteristics (disease burden, baseline cytokines, lactate dehydrogenase levels, HLA haplotype, and prior exposure to immune checkpoint inhibitors), phenotypic features of transferred T cells (total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and target antigenic scope), and other treatment-related factors (lymphodepleting chemotherapy and postinfusion administration of interleukin-2). Key findings include: - High tumor mutational burden (TMB) and neoantigen load are strong predictors of response, even after progression on immune checkpoint inhibitors. - Baseline lactate dehydrogenase (LDH) levels and disease burden are associated with poorer outcomes. - Prior systemic therapies, particularly anti-PD-1 antibodies, do not significantly impact response likelihood. - Baseline serum cytokines and circulating factors, such as IL-9, may influence response. - Short pre-rapid expansion protocol (REP) culture times and high absolute cell counts are strong predictors of response. - TIL antitumor reactivity and phenotype-related parameters, such as CD8:CD4 ratio and exhaustion marker expression, are also important. - The interaction between TIL and the host immune microenvironment is complex and influenced by various factors. The review highlights the need for further research to optimize patient selection and improve the efficacy of TIL therapy.