Iron and oxygen deficiencies are common features in pathophysiological conditions such as is-chemia, neurological diseases, and cancer. Cellular adaptive responses to such deficiencies include repression of mitochondrial respiration as well as promotion of angiogenesis and cell cycle con-trol. We applied a systematic proteomics analysis to determine the global proteomic changes caused by acute hypoxia, chronic and acute iron deficiency (ID) in hippocampal neuronal cells. Our analysis identified over 8600 proteins, revealing similar and differential effects of each treatment on activation and inhibition of pathways regulating neuronal development. In addition, com-parative analysis of ID-induced proteomics changes in cultured cells and transcriptomic changes in the rat hippocampus identified common altered pathways, indicating specific neuronal effects. Taken together, our study identified diverse signaling networks that were differentially regulated by hypoxia and ID in neuronal cells.