Globally, tomatoes hold great economic importance, particularly among temperate zones of southeastern countries of Asia. Notable production losses could result from drought stress conditions. Significant work is being done to enhance tolerance to these agriculturally important varieties of tomato including traditional breeding to novel methods. However, only some genes responsible for drought tolerance processes have been recognized until now. Thus, more studies are needed for contributing the separation and functional characterization of tolerance against abiotic stress for improvement of salinity and drought stress tolerance by genetic modification. Recently, techniques such as grafting, use of plant biostimulants and microbiome engineering are introduced to ameliorate drought tolerance in tomato, which are also safe toward the environment. This chapter elucidates the economic significance and responses of tomato against drought stress. The crucial role of gene modification and genetic engineering, especially microbiome engineering, to fight with drought stress will also be discussed. A brief conception of physiological and productive losses due to drought stress and plant’s natural defense mechanism in such stress will be investigated.