The genomic era witnessed the deciphering of molecular mechanisms underlying human gastric cancer (GC) that paved the way to specifically target key molecules or proteins involved in disease progression. A multifactorial disease, GC has a host of other factors that influence its initiation and progression such as age, gender, severe exposure to several environmental pressures, and inadequate diet. These aspects lead to changes at the molecular level that reflect at the protein level, thereby contributing to cancer. Targeting such specific proteins, widely referred to as targeted therapy (TT), is actively sought because it promises treatment precision. Several clinical trials are underway with candidate drugs and in combination with other lines of treatment such as chemotherapy and radiation therapy, for which results are varied. This review summarizes strategies that are involved in GC treatment, delving deeply into TT approaches (based on small molecules) that have already reached the clinic or are currently in clinical trials.