Chemotherapy is a common treatment for women with ovarian cancer, and many women treated with chemotherapy experience cognitive dysfunction. However, few studies have investigated the mechanisms of chemotherapy-related cognitive impairment in women with ovarian cancer. The goal of this study was to assess the relationships among neurovascular coupling, iron levels and cognitive functions in women with ovarian cancer after first-line chemotherapy. Simultaneous fNIRS and EEG data were collected in women diagnosed with advanced stage ovarian cancer at baseline (N = 13) and after 3-9 rounds of chemotherapy (N = 8). The attentional network task (ANT) was administered for neurocognitive evaluation. Blood iron levels were measured using standard clinical assays. In parallel, similar concurrent fNIRS-EEG data were acquired in a group of 10 healthy participants in a test-retest design. Cognitive performance declined, as indicated by decreases in ANT sub scores after chemotherapy. Blood iron biomarkers indexing oxygen transport also declined and were related to decreases in the ANT sub scores. Both fNIRS and EEG data responses were shown to have excellent reliability in the healthy subjects, while cancer patients showed significant decreases in oxygenated hemoglobin response in fNIRS, despite no changes in EEG responses after chemotherapy. A significant dose relationship was also found in the changes of fNIRS responses. Our data indicate that chemotherapy produced cognitive deficits and decreases in the oxygenated hemoglobin response and that these may be related to reduced oxygen transport capacity. Results also suggest the utility of using fNIRS-EEG to monitor the progression of cognitive impairment and characterize those mechanisms.