Gastric cancer (GC) is one of the most common malignancies worldwide. There has been no efficient therapy for stage IV GC patients due to this disease's heterogeneity and dissemination ability. Despite the rapid advancement of molecular targeted therapies, such as HER2 and immune checkpoint inhibitors, survival of GC patients is still unsatisfactory because the understanding of the mechanism of GC progression is still incomplete. Invasion is the most important feature of GC metastasis, which causes poor mortality in patients. Recently, genomic research has critically deepened our knowledge of which gene products are dysregulated in invasive GC. Furthermore, the study of the interaction of GC cells with the tumor microenvironment has emerged as a principal subject in driving invasion and metastasis. These results are expected to provide a profound knowledge of how biological molecules are implicated in GC development. This review summarizes the advances in our current understanding of the molecular mechanism of GC invasion. We also highlight the future directions of the invasion therapeutics of GC. Compared to conventional therapy using protease or molecular inhibitors alone, multi-therapy targeting invasion plasticity may seem to be an assuring direction for the progression of novel strategies.