Water scarcity is the primary constraint on crop productivity in arid and semiarid tropical areas suffering from climate alterations; in accordance, agricultural systems have to be optimized. Several concepts and strategies should be considered to improve crop yield and quality, particularly in vulnerable regions where such environmental changes cause a risk of food insecurity. In this work, we review two strategies aiming to increase drought stress tolerance: (i) the use of natural genes that have evolved over time and are preserved in crop wild relatives and landraces for drought tolerance breeding using conventional and molecular methods and (ii) exploiting the reservoir of neglected and underutilized species to identify those that are known to be more drought-tolerant than conventional staple crops while possessing other desired agronomic and nutritive characteristics, as well as introducing them into existing cropping systems to make them more resilient to water deficiency conditions. In the past, the existence of drought tolerance genes in crop wild relatives and landraces was either unknown or difficult to exploit using traditional breeding techniques to secure potential long-term solutions. Today, with the advances in genomics and phenomics, there are a number of new tools available that facilitate the discovery of drought resistance genes in crop wild relatives and landraces and their relatively easy transfer into advanced breeding lines, thus accelerating breeding progress and creating resilient varieties that can withstand prolonged drought periods. Among those tools are marker-assisted selection (MAS), genomic selection (GS), and targeted gene editing (clustered regularly interspaced short palindromic repeat (CRISPR) technology). The integration of these two major strategies, the advances in conventional and molecular breeding for the drought tolerance of conventional staple crops, and the introduction of drought-tolerant neglected and underutilized species into existing production systems has the potential to enhance the resilience of agricultural production under conditions of water scarcity.