Climate change poses significant threats to global agriculture, necessitating the development of climate-resilient crops and modern breeding technologies. High-throughput sequencing (HTS) and integrative genomic strategies are at the forefront of this transformation, enabling the identification of novel alleles and optimizing breeding practices. This chapter explores the integration of HTS technologies, such as next-generation sequencing (NGS) and genomic selection (GS), into traditional breeding methods to enhance genetic gain and develop crops capable of withstanding extreme climatic conditions. By leveraging multiparent populations, advanced phenotyping, and rapid breeding techniques like speed breeding (SB), this chapter emphasizes the potential of these innovations to reduce breeding cycle time, increase selection intensity, and advance heritability estimates. The application of machine learning and pan-genomics further enhances the ability to produce robust and adaptable crops, ensuring agricultural productivity and food security in the face of climate change. This chapter concludes by highlighting the transformative impact of HTS on breeding methodologies, advocating for the continued integration of these technologies to sustain global agriculture.