Gastroesophageal cancers are among the most prevalent cancers globally and represent the third leading cause of cancer-related mortality worldwide. Surgical resection remains the primary curative approach for localised and locally advanced stages, but its effectiveness is limited for locally advanced diseases, evidenced by a low 5-year survival rate of around 25%. High relapse rates post-surgery, particularly in Western populations, necessitate the use of neoadjuvant, adjuvant or perioperative strategies involving chemotherapy and radiation to improve surgical outcomes. Neoadjuvant chemoradiation therapy has demonstrated a significant improvement in overall survival. Recent advances have identified several target genes and pathways involved in the pathogenesis and progression of these cancers, leading to the development of targeted drugs, including immunotherapy, anti-HER-2 antibodies and anti-vascular endothelial growth factor receptor antibodies. These targeted therapies are emerging as promising interventions for better patient outcomes and personalised treatment approaches and, therefore, could eventually evolve into a novel therapeutic regimen for gastroesophageal cancer.