The rapid development of multiome (transcriptome, proteome, cistrome, imaging, and regulome)-wide association study methods have opened new avenues for biologists to understand the susceptibility genes underlying complex diseases. Thorough comparisons of these methods are essential for selecting the most appropriate tool for a given research objective. This review provides a detailed categorization and summary of the statistical models, use cases, and advantages of recent multiome-wide association studies. In addition, to illustrate gene-disease association studies based on transcriptome-wide association study (TWAS), we collected 478 disease entries across 22 categories from 235 manually reviewed publications. Our analysis reveals that mental disorders are the most frequently studied diseases by TWAS, indicating its potential to deepen our understanding of the genetic architecture of complex diseases. In summary, this review underscores the importance of multiome-wide association studies in elucidating complex diseases and highlights the significance of selecting the appropriate method for each study.