Cisplatin is commonly used in combination with other cytotoxic agents as a standard treatment regimen for a variety of solid tumors, such as lung, ovarian, testicular, and head and neck cancers. However, the effectiveness of cisplatin is accompanied by toxic side effects, for instance, nephrotoxicity and neurotoxicity. The response of tumors to cisplatin treatment involves multiple physiological processes, and the efficacy of chemotherapy is limited by the intrinsic and acquired resistance of tumor cells. Although enormous efforts have been made toward molecular mechanisms of cisplatin resistance, the development of omics provides new insights into the understanding of cisplatin resistance at genome, transcriptome, proteome, metabolome and epigenome levels. Mechanism studies using different omics approaches revealed the necessity of multi-omics applications, which provide information at different cellular function levels and expand our recognition of the peculiar genetic and phenotypic heterogeneity of cancer. The present work systematically describes the underlying mechanisms of cisplatin resistance in different tumor types using multi-omics approaches. In addition to the classical mechanisms such as enhanced drug efflux, increased DNA damage repair and changes in the cell cycle and apoptotic pathways, other changes like increased protein damage clearance, increased protein glycosylation, enhanced glycolytic process, dysregulation of the oxidative phosphorylation pathway, ferroptosis suppression and mRNA m6A methylation modification can also induce cisplatin resistance. Therefore, utilizing the integrated omics to identify key signaling pathways, target genes and biomarkers that regulate chemoresistance are essential for the development of new drugs or strategies to restore tumor sensitivity to cisplatin.