The article discusses the challenges of treating 'cold' tumors, which are resistant to immune checkpoint inhibitors (ICIs) due to limited T cell infiltration and immune evasion mechanisms. It highlights the importance of understanding tumor immunology to develop effective cancer treatments. 'Cold' tumors are characterized by poor T cell infiltration, low PD-L1 expression, and a low tumor mutational burden, while 'hot' tumors have high T cell infiltration and favorable responses to ICIs. The article explores various mechanisms of immune escape in 'cold' tumors, including defective antigen presentation, impaired T cell infiltration, vascular abnormalities, and oncogenic pathway activation. It also discusses therapeutic strategies to overcome 'cold' tumors, such as dual ICIs, CAR-T cell therapy, CAR-NK cell therapy, T cell redirecting bispecific antibodies, cancer vaccines, oncolytic viruses, macrophage-targeted therapy, radiotherapy, and chemotherapy combined with ICIs. These strategies aim to enhance T cell infiltration, modulate the tumor microenvironment, and improve the efficacy of immunotherapy. The article emphasizes the need for combined therapeutic approaches to address the complex interplay of immune evasion mechanisms in 'cold' tumors.The article discusses the challenges of treating 'cold' tumors, which are resistant to immune checkpoint inhibitors (ICIs) due to limited T cell infiltration and immune evasion mechanisms. It highlights the importance of understanding tumor immunology to develop effective cancer treatments. 'Cold' tumors are characterized by poor T cell infiltration, low PD-L1 expression, and a low tumor mutational burden, while 'hot' tumors have high T cell infiltration and favorable responses to ICIs. The article explores various mechanisms of immune escape in 'cold' tumors, including defective antigen presentation, impaired T cell infiltration, vascular abnormalities, and oncogenic pathway activation. It also discusses therapeutic strategies to overcome 'cold' tumors, such as dual ICIs, CAR-T cell therapy, CAR-NK cell therapy, T cell redirecting bispecific antibodies, cancer vaccines, oncolytic viruses, macrophage-targeted therapy, radiotherapy, and chemotherapy combined with ICIs. These strategies aim to enhance T cell infiltration, modulate the tumor microenvironment, and improve the efficacy of immunotherapy. The article emphasizes the need for combined therapeutic approaches to address the complex interplay of immune evasion mechanisms in 'cold' tumors.