In line with the advances in high-throughput technologies, multiple omic datasets have accumulated to study biological systems and diseases coherently. No single omics data type is capable of fully representing cellular activity. The complexity of the biological processes arises from the interactions between omic entities such as genes, proteins, and metabolites. Therefore, multi-omic data integration is crucial but challenging. The impact of the molecular alterations in multi-omic data is not local in the neighborhood of the altered gene or protein; rather, the impact diffuses in the network and changes the functionality of multiple signaling pathways and regulation of the gene expression. Additionally, multi-omic data is high-dimensional and has background noise. Several integrative approaches have been developed to accurately interpret the multi-omic datasets, including machine learning, network-based methods, and their combination. In this review, we overview the most recent integrative approaches and tools with a focus on network-based methods. We then discuss these approaches according to their specific applications, from disease-network and biomarker identification to patient stratification, drug discovery, and repurposing.