The East Sea region presents a prolific and underexplored source of marine microbial natural products with immense potential for drug discovery and biotechnological applications. The unique ecological conditions of the East Sea, from its diverse Vietnamese coastal ecosystems to remote archipelagos and deep-sea habitats, foster microbial communities capable of producing structurally unique and potent bioactive compounds. This chapter delves into the bioprospecting efforts within this region by focusing on marine microbes, such as bacteria and fungi, and revealing their capacity to produce diverse bioactive compounds, such as alkaloids, peptides, polyketides, terpenoids and steroids. These secondary metabolites exhibit significant pharmacological properties, including antimicrobial, anticancer and anti-inflammatory activities, addressing pressing medical challenges like antibiotic resistance and cancer therapy. Furthermore, the chapter underscores the role of advanced molecular biology and cultivation techniques in isolating and characterizing novel metabolites from marine microorganisms. It also highlights key discoveries, including compounds with promising therapeutic applications, emphasizing the East Sea's importance as a hotspot for natural product research. Moreover, it advocates sustainable and systematic exploration to unlock the full potential of this biodiverse region. By bridging marine ecology and pharmacology, this research enriches the global repository of therapeutic agents and contributes to addressing unmet medical needs in an environmentally conscious manner.