BACKGROUND Bone morphogenetic proteins (BMPs) are widely involved in cancer development. However, a wealth of conflicting data raises the question of whether BMPs serve as oncogenes or as cancer suppressors. MATERIAL AND METHODS By integrating multi-omics data across cancers, we comprehensively analyzed the genomic and pharmacogenomic landscape of BMP genes across cancers. RESULTS Surprisingly, our data indicate that BMPs are globally downregulated in cancers. Further genetics and epigenetics analyses show that this abnormal expression is driven by copy number variations, especially heterozygous amplification. We next assessed the BMP-associated pathways and demonstrated that they suppress cell cycle and estrogen hormone pathways. Bone morphogenetic protein interacts with 58 compounds, and their dysfunction can induce drug sensitivity. CONCLUSIONS Our results define the landscape of the BMP family at a systems level and open potential therapeutic opportunities for cancer patients.