Tumor immunotherapy leverages the body’s immune system to target and eradicate cancer cells, offering a crucial treatment for patients unresponsive to surgery or conventional therapies. Despite its potential, the effectiveness of immunotherapy is often hindered by T cell exhaustion within the tumor microenvironment, leading to diminished immune response and tumor progression. Based on these challenges, exploring the role of progenitor exhausted T cells (Tpex) in overcoming immune resistance is essential for advancing immunotherapeutic strategies and improving clinical outcomes.