Musk, secreted by the musk gland of adult male musk-secreting mammals, holds significant pharmaceutical and cosmetic potential. However, understanding the molecular mechanisms of musk secretion remains limited, largely due to the lack of comprehensive multiomics analyses and available platforms for relevant species, such as muskrat (Ondatra zibethicus Linnaeus) and Chinese forest musk deer (Moschus berezovskii Flerov). We generated chromosome-level genome assemblies for the 2 species of muskrat (Ondatra zibethicus Linnaeus) and musk deer (Moschus berezovskii Flerov), along with 168 transcriptomes from various muskrat tissues. Comparative analysis with 11 other vertebrate genomes revealed genes and amino acid sites with signs of adaptive convergent evolution, primarily linked to lipid metabolism, cell cycle regulation, protein binding, and immunity. Single-cell RNA sequencing in muskrat musk glands identified increased acinar/glandular epithelial cells during secretion, highlighting the role of lipometabolism in gland development and evolution. Additionally, we developed MuskDB (http://muskdb.cn/home/), a freely accessible multiomics database platform for musk-secreting mammals. The study concludes that the evolution of musk secretion in muskrats and musk deer is likely driven by lipid metabolism and cell specialization. This underscores the complexity of the musk gland and calls for further investigation into musk secretion-specific genetic variants.