Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes. HRD tumors are characterized by trisomy of chromosomes 3, 5, 7, 9, 11, 15, 19, and/or 21. Non-HRD tumors harbor IGH translocations, mainly t(4;14), t(6;14), t(11;14), t(14;16), and t(14;20). Secondary events participate to the tumor progression and consist in secondary translocation involving MYC, copy number variations (CNV) and somatic mutations (such as mutations in KRAS, NRAS, BRAF, P53). Moreover, the dissection of clonal heterogeneity helps to understand the evolution of the disease. The following review provides a comprehensive review of the genomic landscape in MM.