What genetic mutations influence breast cancer risk?, Which gene expression signatures better define prognostic and predictive subtypes?, What are the mechanisms of resistance to targeted therapies? and How can we improve early detection and screening? illustrate the broad impact of oncogenomics in addressing critical breast cancer research and clinical practice questions. Advances in oncogenomics have been propelled by innovations of next-generation sequencing technologies (NGS) and bioinformatics tools for analyzing omics data (genomics, epigenomics and transcriptomics) from tumor bulk to single cell levels. Transcriptomic profiling allows comprehensive exploration of gene expression patterns, revealing key insights into the molecular mechanisms underlying cancer development, progression, and response to therapy. Bulk RNA-seq methods provide a global view of the tumor transcriptome and have revolutionized our understanding of tumor heterogeneity by identifying distinct intrinsic tumor subtypes and revealing the clinical implications of tumor-infiltrating immune cells. By capturing the transcriptomes of individual cells, scRNA-seq provides unprecedented resolution, enabling the characterization of rare cell populations, identification of novel cell types, and the detection of dynamic cellular states during tumor progression. Spatial omics technologies allow researchers to map the distribution of molecular features (RNA, proteins, and metabolites) within the native spatial context, highlighting their crucial role in understanding the complexities of an intricate spatially organized ecosystem, the tumor tissue. Here, several state-of-the-art omics approaches are discussed, providing a comprehensive insight into the field, including the identification of mutational processes, cell signaling, immune cell profiling, and prediction of the immunotherapy response.