Cassava is a staple food crop that ensures food security and is a source of income generation for poor farmers in the tropics of many Asian and African countries that are highly prone to harsh and unfavorable environments especially in the context of climate changes. Improving tolerance to abiotic stresses such as drought in this crop is a big challenge as it has substantial tolerance to drought compared to other crops. There has been little investment in employing advanced breeding technology for genetic improvement of cassava, though we have now an increased access to emerging advanced tools in genomics, transcriptomics, phenomics, proteomics, and metabolomics for that can enhance our capacity to understand stress responses and tolerance in plants. In this chapter, we have reviewed challenges and opportunities for improving productivity of cassava by integrating omics with conventional breeding. The chapter highlights efforts and vision of International Center for Tropical Agriculture (CIAT; http://www.ciat.cgiar.org) toward a comprehensive evaluation of germplasm, establishment of the transformation and phenotyping platform, and development of genomic tools for deriving the requisite information for developing effective strategies for molecular breeding for high-yield and high-value cassava under stress conditions. The chapter also deals with possible strategies to accelerate development of elite cassava cultivars by integration of the advanced technologies.