Both nitroreductase and the folate receptor are highly expressed in hypoxic tumors. The folate receptor is a potential target for tumors, and nitroreductase can selectively turn on the fluorescence of probes by reducing the nitro group to an amino group. Karan et al. (Karana, S., Cho, M., Lee, H., Lee, H., Park, H., Sundararajan, M., Sessler, J., and Hong, K. Near-infrared fluorescent probe activated by nitroreductase for in vitro and in vivo hypoxic tumor detection. J. Med. Chem. 2021) developed a near-infrared fluorescent probe for hypoxia tumor imaging analysis in vitro and in vivo using folate as the targeting site. This promising strategy may promote advances in precision diagnosis and treatment models of malignant tumors. This Viewpoint looks ahead to new possibilities rendered by their studies.