The climate change-associated abnormal weather patterns negatively influences the productivity and performance of farm animals. Heat stress is the major detrimental factor hampering production, causing substantial economic loss to the livestock industry. Therefore, it is important to identify heat-tolerant breeds that can survive and produce optimally in any given environment. To achieve this goal, a clearer understanding of the genetic differences and the underlying molecular mechanisms associated with climate change impacts and heat tolerance are a prerequisite. Adopting next-generation biotechnological and statistical tools like whole transcriptome analysis, whole metagenome sequencing, bisulphite sequencing, genome-wide association studies (GWAS), and selection signatures provides an opportunity to achieve this goal. Through these techniques, it is possible to identify permanent genetic markers for heat tolerance, and by incorporating those markers in marker-assisted breeding selection, it is possible to achieve the target of breeding for heat tolerance in livestock. This review gives an overview of the recent advancements in assessing heat tolerance in livestock using such ‘omics’ approaches and statistical models. The salient findings from this research highlighted several candidate biomarkers that have the potential to be incorporated into future heat-tolerance studies. Such approaches could revolutionise livestock production in the changing climate scenario and support the food demands of the growing human population.