ContextCotton production is influenced by water and nitrogen (N). However, the magnitude and direction of seed cotton yield, water use efficiency (WUE) and N use efficiency (NUE) responses to water and N inputs varied among the available studies due to different experimental and environmental factors (such as cotton varieties, climate types and irrigation systems). ObjectiveTo quantify the relationships between water and N inputs and seed cotton yield, WUE and NUE and estimate the potential for water and N optimization, 61 studies conducted in 9 countries were collected to establish a meta database. MethodsThe relationships between water and N inputs and the interesting response variables were studied using a linear mixed-effects model in a partially restricted dataset. And the potential for water and N optimization was discussed using a meta-analysis in three classified datasets. Results and conclusionsTotal water and N inputs had significant positive effects on seed cotton yield. WUE was negatively related to water input and positively related to N input, while NUE was positively related to water input and unrelated to N input. Negative interaction between water and N inputs existed in WUE and NUE, and the interaction was relatively large in NUE compared to in WUE. Reducing over-optimal water input to optimal may increase seed cotton yield by 12.3%, WUE by 25.0% and NUE by 2.2%. Similarly, reducing over-optimal N input to optimal may increase seed cotton yield and WUE by about 16.0% and NUE by 44.6%. There was great potential for optimizing water and N inputs in arid and hot desert climate (BWh) comparing with in arid and cold desert climate (BWk) and arid and cold steppe climate (BSk), and the seed cotton yield, WUE and NUE can be increased by up to around 35.0%, 16.6% and 34.5%, respectively. Surface irrigation had greater potential to optimize water and N inputs than drip irrigation, and the seed cotton yield and WUE can be increased by up to 50.7% and 43.0%, respectively. SignificanceThe findings provided suggestions for improving irrigation and fertilization in cotton production.