Precision medicine and multi-omics have provided new methods for cancer diagnosis and treatment, holding the potential to significantly improve the therapeutic effects and quality of life for cancer patients. With the advancement of next-generation sequencing technology and mass spectrometry-based multi-omics detection techniques, the application of genomics, transcriptomics, proteomics, metabolomics, and microbiomics has helped us gain a deeper understanding of the molecular mechanisms of cancer, identify potential therapeutic targets and biomarkers, and thus promote personalized cancer treatment. Moreover, the integrated analysis of multi-omics data provides comprehensive evidence for precision medicine, aiding in revealing the pathogenesis of diseases and providing a scientific basis for cancer prediction, prevention, diagnosis, treatment, and prognosis assessment. This review summarizes the progress in the application of precision medicine and multi-omics technologies in immunoradiotherapy, compares the advantages of precision medicine and multi-omics technologies over traditional detection techniques in terms of biomarker identification and clinical decision-making accuracy, and analyzes the existing problems and challenges with the aim of providing new ideas to promote research in immunoradiotherapy.