Fomitopsis betulina, as a macrofungus with both medicinal and dietary applications, is renowned for its rich content of bioactive substances. The recent advancements in research have significantly enhanced our understanding of its polysaccharides, cellulose-degrading enzymes, and wide range of secondary metabolites. This paper provides a comprehensive review of the artificial cultivation techniques and the chemical profiling of over 100 secondary metabolites identified in F. betulina, including terpenoids, phenols, and various other classes. These compounds exhibit notable pharmacological activities, such as anti-cancer, anti-inflammatory, antimicrobial, antiviral, and anti-malarial effects. Moreover, this review delves into the genomic analysis of F. betulina, focusing on the prediction and classification of terpene synthases, which play a crucial role in the biosynthesis of these bioactive compounds. This insight is instrumental for potentially facilitating future biochemical studies and pharmaceutical applications. Through this review, we aim to solidify the foundation for future in-depth studies and the development of new drugs derived from this promising natural resource.