Natural killer (NK) cell functions and their responsiveness towards pathological treats, including infection and cancer, is determined by both systemic and immediate environmental cues sensed at the cellular level. Multiple sensors have evolved to operate within the cells and transform microenvironmental information into cellular adaptation. How such sensors mechanistically co-opt to fine-tune NK cell competency and their actual output is so far underexplored. We have previously shown that conditional deletion of transcriptional factor HIF1α (hypoxia inducible factor 1 subunit alpha), sensor for hypoxia, led to NK cell-dependent control of growth of subcutaneous lymphoma in mice. Here, we show that hindering effects of hypoxia are differentially hard-wired through HIF1α. Namely, the hypoxia-HIF1α-axis regulated NK cell oxidative metabolism and the response to IL-12/18 through transcriptional regulation. However, IFN-γ production induced by IL-12/IL-18 was preserved under hypoxia, despite hypoxia-HIF-1α-driven transcriptional repression of this pathway. This effect could be attributed to the sensing of the environmental tryptophan and the activation of the Aryl-hydrocarbon receptor (AhR) that magnified the engagement of the mTORC1-cMyc-IkBζ pathway upon stimulation with IL-12/18, leading to elevated IFN-γ expression. Finally, we show that NK cells harmonized AhR- and HIF-1α-signals through defined transcriptional modules, whose signatures can be detected in alike microenvironments in vivo, such as in solid tumor tissue. Together, we show that NK cells functions can be differentially affected in complex microenvironments and can be fine-tuned through regulatory networks controlled by defined sensors, which provide superordinate checkpoints to manage NK cell outputs.