The livestock sector, a crucial source of revenue and global food security, is facing serious challenges due to climate change driven by global warming. This leads to serious effects on animal health and productivity, making it difficult for the livestock industry to meet the global demand and sustain the livelihoods of farmers. The main factor affecting livestock’s productivity is heat stress. However, animals develop various adaptive mechanisms to cope with the effects of heat stress. Cellular and molecular responses act as key defense mechanisms, enabling animals adapt to environmental changes. The recent advancements in molecular biology have opened up opportunities for extensive research on epigenetics, which has a key role in regulating gene expression in animals in response to environmental stimuli. Such studies have gained considerable attention regarding heat acclimation in animals due to the fact that epigenetic mechanisms have been recognized as key players in long-term adaptation to high temperatures in farm animals. This review summarizes the different mechanisms and methodologies used to assess heat stress-associated epigenetic changes, including DNA methylation, which is an extensively studied epigenetic regulatory mechanism in relation to gene expression. The review also highlights the mechanisms and regulation of adaptation to heat stress in animals and collates information related to various epigenetic markers to assess the heat stress response, thereby aiding in improving thermal resilience in animals.

Given livestock’s crucial role in global food security and economic stability, the alarming threat of climate change calls for the implementation of effective mitigation strategies for climate-resilient livestock production. Management and nutritional strategies offer temporary relief, whereas genetic approaches represent a permanent solution. The role of genetic tools in enabling the development of climate-resilient livestock breeds is widely recognized. Genetic tools like microarrays, RNA-seq, omics, and GWAS can improve the understanding of livestock’s climate adaptability at a molecular level. These tools facilitate the identification of biomarkers for thermo-tolerance, bordering on climate-resilient livestock breeding. Among them, studies employing genome-wide association studies (GWAS) have increased in recent years. GWAS have the potential to improve the genetic basis of thermo-tolerance in heat-stressed livestock populations. GWAS have been used to identify candidate genes for complex and economically important traits in livestock. These include growth, reproduction, disease resistance, milk, meat, and wool production traits under heat stress conditions. This makes GWAS a useful tool for identifying biomarkers that can be incorporated in breeding programs through marker-assisted selection (MAS). The integration of these potential biomarkers into selection and breeding programs would allow GWAS to substantially refine breeding strategies, thereby advancing the climate-resilient potential and sustainability of the livestock sector. Furthermore, GWAS, when utilized along with emerging technologies like Artificial Intelligence (AI), machine learning (ML), and deep learning (DL) for genomic prediction, can predict genetic aspects of livestock adaptation more efficiently and precisely. Thus, future studies should focus on integrated modeling approaches for improving the climate resilience of livestock without jeopardizing their production potential. Such an effort will contribute to sustainable livestock production as well as ensure food security for the growing human population amid changing climate conditions.