The Hippo pathway is a critical regulator of cell fate, function, and survival, with dysregulation commonly observed in cancer. YAP/TAZ, downstream effectors of the Hippo pathway, are frequently hyperactivated in cancer, promoting tumor growth by driving cell proliferation, survival, and metastasis. However, YAP/TAZ also exhibit tumor-suppressive functions in some cell types, complicating their role as therapeutic targets. Systemic inhibition of YAP/TAZ may have unpredictable effects due to their dual roles in different cellular contexts. This review discusses the complex roles of the Hippo pathway in distinct tumor and tumor-associated cells, the impact of YAP/TAZ inhibition on tumor growth, and current developments in YAP/TAZ inhibitors. YAP/TAZ-TEAD inhibitors have shown promise in preclinical models, particularly in cancers like mesothelioma and NF2 mutant sarcoma, where YAP/TAZ are hyperactivated. These inhibitors can reduce tumor growth by blocking pro-tumoral functions in cancer cells and non-cancer cells. However, their efficacy in cancers without Hippo pathway mutations is uncertain. Systemic inhibition may also affect normal cells, potentially triggering unintended outcomes. For example, YAP/TAZ may be required for tumor-suppressive functions in tumor-associated cells, leading to tumor growth despite YAP/TAZ activity in cancer cells. YAP/TAZ activation in cancer cells promotes tumor growth by modulating immune cells, angiogenesis, and metastasis. In macrophages, YAP/TAZ activation promotes M2-like macrophages, which support tumor growth. In T-cells, YAP/TAZ inhibition enhances antitumor immunity by improving T-cell function and reducing Treg activity. In fibroblasts, YAP/TAZ activation promotes tumor growth by stiffening the tumor microenvironment. In endothelial cells, YAP/TAZ activation drives angiogenesis, essential for tumor growth. Conversely, YAP/TAZ can act as tumor suppressors in some cancers, such as breast and colon cancers, where their activation induces cell death and suppresses tumor growth. YAP/TAZ activation in cancer cells can also enhance immune surveillance by promoting the production of exosomes that activate T-cells and B-cells. In immune cells, YAP/TAZ activation can suppress tumor growth by promoting antitumor immune responses. Systemic inhibition of YAP/TAZ-TEAD may have complex effects, depending on the cellular context. While it can enhance antitumor immunity in some cases, it may also promote tumor growth if YAP/TAZ are required for tumor-suppressive functions in normal cells. Combination therapies with YAP/TAZ-TEAD inhibitors may improve efficacy by reducing therapy resistance and enhancing immune checkpoint inhibitor responses. However, predicting the outcomes of YAP/TAZ-TEAD inhibition remains challenging due to theThe Hippo pathway is a critical regulator of cell fate, function, and survival, with dysregulation commonly observed in cancer. YAP/TAZ, downstream effectors of the Hippo pathway, are frequently hyperactivated in cancer, promoting tumor growth by driving cell proliferation, survival, and metastasis. However, YAP/TAZ also exhibit tumor-suppressive functions in some cell types, complicating their role as therapeutic targets. Systemic inhibition of YAP/TAZ may have unpredictable effects due to their dual roles in different cellular contexts. This review discusses the complex roles of the Hippo pathway in distinct tumor and tumor-associated cells, the impact of YAP/TAZ inhibition on tumor growth, and current developments in YAP/TAZ inhibitors. YAP/TAZ-TEAD inhibitors have shown promise in preclinical models, particularly in cancers like mesothelioma and NF2 mutant sarcoma, where YAP/TAZ are hyperactivated. These inhibitors can reduce tumor growth by blocking pro-tumoral functions in cancer cells and non-cancer cells. However, their efficacy in cancers without Hippo pathway mutations is uncertain. Systemic inhibition may also affect normal cells, potentially triggering unintended outcomes. For example, YAP/TAZ may be required for tumor-suppressive functions in tumor-associated cells, leading to tumor growth despite YAP/TAZ activity in cancer cells. YAP/TAZ activation in cancer cells promotes tumor growth by modulating immune cells, angiogenesis, and metastasis. In macrophages, YAP/TAZ activation promotes M2-like macrophages, which support tumor growth. In T-cells, YAP/TAZ inhibition enhances antitumor immunity by improving T-cell function and reducing Treg activity. In fibroblasts, YAP/TAZ activation promotes tumor growth by stiffening the tumor microenvironment. In endothelial cells, YAP/TAZ activation drives angiogenesis, essential for tumor growth. Conversely, YAP/TAZ can act as tumor suppressors in some cancers, such as breast and colon cancers, where their activation induces cell death and suppresses tumor growth. YAP/TAZ activation in cancer cells can also enhance immune surveillance by promoting the production of exosomes that activate T-cells and B-cells. In immune cells, YAP/TAZ activation can suppress tumor growth by promoting antitumor immune responses. Systemic inhibition of YAP/TAZ-TEAD may have complex effects, depending on the cellular context. While it can enhance antitumor immunity in some cases, it may also promote tumor growth if YAP/TAZ are required for tumor-suppressive functions in normal cells. Combination therapies with YAP/TAZ-TEAD inhibitors may improve efficacy by reducing therapy resistance and enhancing immune checkpoint inhibitor responses. However, predicting the outcomes of YAP/TAZ-TEAD inhibition remains challenging due to the