Systems biology is a rapidly growing field that aims to understand the complex interplay between biological systems at various levels and how they integrate into a unified whole. Integrating various multi-omics data from multiple sources such as livestock genomics, transcriptomics, proteomics, metabolomics, and other omics to understand the underlying mechanisms of intricate biological processes is one of the key challenges in systems biology. In livestock research and veterinary science, a systems biology approach can provide novel insights into the biology of domesticated animals, including their health, welfare, and productivity. This chapter aims to provide an overview of the principles of systems biology, as well as the methods for integrating multi-omics data. Here, we discuss the challenges and opportunities of applying systems biology in livestock research and veterinary science by focusing on the identification of key genes/proteins and biomarkers for disease diagnosis, prediction, and treatment. Additionally, this chapter explores the application of systems biology approaches in livestock using the domesticated pig as a model system, in addition to providing examples of successful integrative omics studies concerning porcine reproductive and respiratory syndrome virus (PRRSV). Finally, we discuss the future perspectives and potential advancements of systems biology and multi-omics integration (MOI) in livestock research and veterinary science.