A personalized approach is a promising tool for malignant neoplasm (MN) treatment. Gaining success and benefit assessment of this approach were considerably facilitated by the implementation of the new generation sequencing techniques which allow to obtain comprehensive information on the tumor genome and transcriptome state with identifying potential biomarkers and targets for directed drug action. Despite the exponential growth in the number of sequenced tumor genomes, some of them are not subject of active clinical studies, although obviously and increasingly require optimization of current treatment regimens. One of these pathologies is multiple myeloma (MM). Considerable advances in its diagnosis and treatment have substantially increased survival rates. However, MM cannot be removed from the list of fatal diseases, yet. It is a neoplasm which needs to be further studied and explored for implementation of new treatment strategies, most of which would be based on pheno- and genotypic characteristics of tumor cells. The present review deals with the state of the art in the study of the MM molecular genetic profile, minimal residual disease (MRD) monitoring as well as potentials of the new generation sequencing for MRD diagnosis, prognosis, estimation, and search for predictors aimed at chemotherapy optimization.