The combination of drought stress and high tropospheric ozone conditions poses a significant threat to crop yield and global food security. This chapter provides an in-depth analysis of the individual effects of drought stress and ozone on crop productivity, as well as the complex interactions and different responses (synergistic/additive/antagonistic) that occur when these stressors act together. The chapter discusses the physiological, biochemical, and morphological mechanisms underlying the combined effect, emphasizing the oxidative stress, water relations, and photosynthetic impairment induced by the interaction of drought stress and ozone. Furthermore, the chapter explores the implications for crop productivity and food security, highlighting the yield losses, vulnerability of certain regions, and the importance of adaptive strategies. The conclusion emphasizes the need for multidisciplinary approaches and the implementation of sustainable practices to mitigate the combined effect and ensure food security in a changing climate.