Over half of patients diagnosed with high grade serous ovarian cancer will die within five years, highlighting the need for therapy innovation. Engineering T cells to target proteins uniquely overexpressed in tumors has the potential to limit tumor growth without toxicity—mesothelin (Msln) is a rational immunotherapy target as it contributes to the malignant/invasive phenotype and has limited expression in healthy cells. T cells were engineered to express a high-affinity Msln-specific T cell receptor (TCRMsln) and adoptively transferred into a disseminated ID8VEGF murine model, which recapitulates many features of human ovarian cancer. TCRMsln+ T cells preferentially accumulated within established tumors, delayed tumor growth, and significantly prolonged survival. However, T cell persistence and anti-cancer activity were limited by elements in the tumor microenvironment (TME), including Fas Ligand (FasL) that can induce apoptosis in infiltrating lymphocytes expressing Fas receptor (Fas). To overcome this potential T cell evasion mechanism, we generated a panel of immunomodulatory fusion proteins (IFPs) containing the Fas extracellular binding domain fused to a co-stimulatory domain, replacing the natural death domain. Relative to T cells modified with only TCRMsln, T cells that expressed both TCRMsln and a Fas IFP preferentially infiltrated tumors and expanded/persisted in the TME of tumor-bearing mice. Moreover, adoptive immunotherapy with TCRMsln+IFP+ T cells significantly prolonged survival in tumor-bearing mice, relative to TCRMsln+ only T cells. As many solid tumors overexpress FasL, IFPs may provide an opportunity to enhance engineered adoptive T cell therapy against many malignancies.