The article discusses the collaborative and crosstalk mechanisms between the transcription factors NF-κB and STAT3 in cancer development. Both factors are widely expressed and play crucial roles in various physiological processes, including development, differentiation, immunity, metabolism, and cancer. They are rapidly activated in response to various stimuli and control the expression of genes involved in anti-apoptosis, proliferation, and immune response. The interaction between NF-κB and STAT3 is particularly significant in the tumor microenvironment, where cytokines induced by NF-κB in immune cells lead to STAT3 activation in both malignant and immune cells. While STAT3 exerts oncogenic functions in malignant and pre-malignant cells, it may also suppress tumor promotion through its anti-inflammatory effects in inflammatory cells. The article highlights the complex interactions between NF-κB and STAT3, including physical interaction, cooperation at gene promoters, and the regulation of each other's activity. Despite these interactions, NF-κB and STAT3 cooperate to promote the development and progression of cancers such as colon, gastric, and liver cancers. The findings suggest that targeting the interplay between NF-κB and STAT3 could be a promising therapeutic strategy for cancer treatment.The article discusses the collaborative and crosstalk mechanisms between the transcription factors NF-κB and STAT3 in cancer development. Both factors are widely expressed and play crucial roles in various physiological processes, including development, differentiation, immunity, metabolism, and cancer. They are rapidly activated in response to various stimuli and control the expression of genes involved in anti-apoptosis, proliferation, and immune response. The interaction between NF-κB and STAT3 is particularly significant in the tumor microenvironment, where cytokines induced by NF-κB in immune cells lead to STAT3 activation in both malignant and immune cells. While STAT3 exerts oncogenic functions in malignant and pre-malignant cells, it may also suppress tumor promotion through its anti-inflammatory effects in inflammatory cells. The article highlights the complex interactions between NF-κB and STAT3, including physical interaction, cooperation at gene promoters, and the regulation of each other's activity. Despite these interactions, NF-κB and STAT3 cooperate to promote the development and progression of cancers such as colon, gastric, and liver cancers. The findings suggest that targeting the interplay between NF-κB and STAT3 could be a promising therapeutic strategy for cancer treatment.