Chronic stress increases metastasis in cancer patients by altering the tumor microenvironment, particularly through neutrophil-mediated changes. The study shows that chronic stress increases lung metastasis from disseminated cancer cells by 2- to 4-fold in mice. Stress significantly alters the lung microenvironment, increasing neutrophil infiltration and fibronectin accumulation, while reducing T cell infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts the normal circadian rhythm of neutrophils and increases neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Digesting NETs with deoxyribonuclease (DNase) I prevents chronic stress-induced metastasis. These findings suggest that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, targeting NETs could be a strategy to prevent metastatic recurrence in cancer patients, many of whom experience chronic stress due to their disease. The study also shows that chronic stress promotes metastasis by affecting neutrophils, which can promote metastasis through mechanisms such as inhibiting T cell-mediated immunosurveillance and forming NETs. Stress-induced NET formation is mediated by glucocorticoids, which alter neutrophil circadian rhythms and promote NET formation. Targeting stress-induced NETs can rescue metastases, as shown by the use of DNase I, which reduces NET levels and prevents metastasis. The study highlights the role of chronic stress in promoting metastasis through the release of glucocorticoids, which induce neutrophil extracellular trap formation and create a pro-metastatic microenvironment. These findings have implications for cancer treatment, suggesting that reducing stress and targeting NETs could be important strategies for preventing metastatic recurrence.Chronic stress increases metastasis in cancer patients by altering the tumor microenvironment, particularly through neutrophil-mediated changes. The study shows that chronic stress increases lung metastasis from disseminated cancer cells by 2- to 4-fold in mice. Stress significantly alters the lung microenvironment, increasing neutrophil infiltration and fibronectin accumulation, while reducing T cell infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts the normal circadian rhythm of neutrophils and increases neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Digesting NETs with deoxyribonuclease (DNase) I prevents chronic stress-induced metastasis. These findings suggest that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, targeting NETs could be a strategy to prevent metastatic recurrence in cancer patients, many of whom experience chronic stress due to their disease. The study also shows that chronic stress promotes metastasis by affecting neutrophils, which can promote metastasis through mechanisms such as inhibiting T cell-mediated immunosurveillance and forming NETs. Stress-induced NET formation is mediated by glucocorticoids, which alter neutrophil circadian rhythms and promote NET formation. Targeting stress-induced NETs can rescue metastases, as shown by the use of DNase I, which reduces NET levels and prevents metastasis. The study highlights the role of chronic stress in promoting metastasis through the release of glucocorticoids, which induce neutrophil extracellular trap formation and create a pro-metastatic microenvironment. These findings have implications for cancer treatment, suggesting that reducing stress and targeting NETs could be important strategies for preventing metastatic recurrence.