Gastric cancer (GC) is the second highest cause of global cancer mortality and particularly prevalent in Asia. Previous research has established that GC is a heterogeneous disease, with each patients' cancer exhibiting distinct genetic and molecular profiles. However, little of these molecular differences currently impact on the clinical management of GC patients, with most patients today being treated with relatively uniform institutional protocols. In this talk, I will describe our progress in integrating genomic databases of GC patients and experimental models to dissect heterogeneous panels of GC patients into discrete subgroups unified by common underlying disease mechanisms. I will present evidence that the molecular heterogeneity of GC is indeed clinically relevant, impacting patient prognosis and response to therapy. Consideration of the underlying heterogeneity of GC should thus be an important factor in the evaluation of both standard and novel therapeutics in GC.