Abstract: It has been a long-standing interest in the biomedical field to delineate pathogen‒host cell interactions. The latest advancements in single-cell analyses with multiomics approaches have begun to revolutionize our understanding of the impact of intratumoral bacteria on tumor development. Recent studies suggest that intratumoral bacteria modulate the communication between tumor cells and surrounding immune cells, which changes tumor progression and plasticity. Thus, a better understanding of the molecular mechanisms underlying intratumor bacteria-elicited pathogen‒host interactions will shed light on targeted interrogation in clinical oncology. This essay highlights recent progress in intratumor bacterial signaling and host cell plasticity control. In addition, we provide perspectives on how the molecular delineation of intratumor bacterial signaling and host cell plasticity control can help precision medicine and novel therapeutic development.