Metastatic castration-resistant prostate cancer (mCRPC) requires new therapeutic strategies. Its immunosuppressive tumor microenvironment (TME) impairs antitumor immunity and induces T-cell exhaustion. Bispecific T-cell engagers (BiTCEs) targeting prostate-specific membrane antigen (PSMA) induce antitumor T-cell activity, while trispecific T-cell engagers (TriTCEs) incorporate additional domains to overcome limitations in a cold TME. T-cell costimulation affects activation, proliferation, survival, memory differentiation, and metabolic function. One study showed that cis delivery of CD3-TCR stimulation and 4-1BB costimulation enhanced T-cell function and NF-κB signaling compared with trans delivery. Another study found that PSMA×CD3 TriTCEs incorporating OX40, 4-1BB, or CD28 promoted T-cell function and tumor immune infiltration. TriTCE-4-1BB and TriTCE-CD28 increased effector memory and CD4+ T-cell proportions more than TriTCE-OX40. Under immunosuppressive conditions, TriTCE-4-1BB showed the lowest proportion of PD-1+TIM-3+ T cells and the greatest tumor suppression and survival prolongation in an advanced tumor xenograft model. These findings suggest that combining TCR and costimulatory signaling in a single antibody may help maintain T-cell function in the TME. However, cis superiority has not been directly validated in TriTCEs. Further preclinical validation, CRS and off-tumor toxicity assessment, and strategies considering patient-specific TME heterogeneity are needed.