Gastric cancer is not among the top 10 cancers in the United States but is a leading cause of cancer death globally. Treatment involves systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy, with a multidisciplinary approach essential. Triplet chemotherapy is now standard for resectable gastric cancer. Molecular subtypes allow for personalized therapy, with biomarkers like microsatellite instability (MSI), PD-L1, HER2, and tumor mutation burden guiding treatment. Research continues for less differentiated subtypes and those without immunotherapy markers. Diagnosis and staging include endoscopy, endoscopic ultrasound, and imaging. Staging laparoscopy is critical for identifying peritoneal disease. MSI testing is increasingly used to guide treatment, with MSI-high tumors showing better outcomes with surgery alone. The MAGIC trial showed improved survival with perioperative chemotherapy in MSI-high patients. The FLOT4-AIO trial demonstrated superior outcomes with FLOT chemotherapy. For localized disease, perioperative chemotherapy is preferred over upfront surgery. The MAGIC trial showed survival benefits with perioperative chemotherapy. The FLOT4-AIO trial showed better outcomes with FLOT. HER2-targeted agents and VEGF inhibition are explored in perioperative settings. Adjuvant chemotherapy is recommended for pathologic T3/T4 or lymph node-positive disease. The CLASSIC trial showed benefits of adjuvant capecitabine and oxaliplatin. Adjuvant chemoradiotherapy has uncertain benefits, with the INT 0116 trial showing OS benefit. Adjuvant chemoradiotherapy is recommended for R1 or R2 resections. Preoperative chemoradiotherapy is a category 2B option. Endoscopic resection is suitable for early-stage cancers with specific criteria. Surgical options include subtotal or total gastrectomy. D2 lymph node dissection is essential for adequate staging. The extent of D1 and D2 lymphadenectomy is critical for staging. Surgical resection is guided by anatomical details and lymph node dissection. Metastatic and unresectable gastric cancer treatment includes cytotoxic agents like fluoropyrimidines, platinum, taxanes, and irinotecan. Combination regimens offer better outcomes. Immunotherapy, including PD-1 inhibitors, is effective in MSI-H and PD-L1-positive tumors. The KEYNOTE-158 trial approved pembrolizumab for MSI-H/dMMR tumors. The KEYNOTE-061 trial showed pembrolizumab's efficacy in PD-L1-positive patients. HER2-positive gastric cancer is treated with trastuzumab, with the ToGA trial establishing its role. New agents like trastuzumab deruxtecan show promise. Antiangiogenic therapy with ramucirumab and combination with immunotherapy is explored. Investigational biomarkers like EGFR and Claudin 18.2 are under study. Liquid biopsyGastric cancer is not among the top 10 cancers in the United States but is a leading cause of cancer death globally. Treatment involves systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy, with a multidisciplinary approach essential. Triplet chemotherapy is now standard for resectable gastric cancer. Molecular subtypes allow for personalized therapy, with biomarkers like microsatellite instability (MSI), PD-L1, HER2, and tumor mutation burden guiding treatment. Research continues for less differentiated subtypes and those without immunotherapy markers. Diagnosis and staging include endoscopy, endoscopic ultrasound, and imaging. Staging laparoscopy is critical for identifying peritoneal disease. MSI testing is increasingly used to guide treatment, with MSI-high tumors showing better outcomes with surgery alone. The MAGIC trial showed improved survival with perioperative chemotherapy in MSI-high patients. The FLOT4-AIO trial demonstrated superior outcomes with FLOT chemotherapy. For localized disease, perioperative chemotherapy is preferred over upfront surgery. The MAGIC trial showed survival benefits with perioperative chemotherapy. The FLOT4-AIO trial showed better outcomes with FLOT. HER2-targeted agents and VEGF inhibition are explored in perioperative settings. Adjuvant chemotherapy is recommended for pathologic T3/T4 or lymph node-positive disease. The CLASSIC trial showed benefits of adjuvant capecitabine and oxaliplatin. Adjuvant chemoradiotherapy has uncertain benefits, with the INT 0116 trial showing OS benefit. Adjuvant chemoradiotherapy is recommended for R1 or R2 resections. Preoperative chemoradiotherapy is a category 2B option. Endoscopic resection is suitable for early-stage cancers with specific criteria. Surgical options include subtotal or total gastrectomy. D2 lymph node dissection is essential for adequate staging. The extent of D1 and D2 lymphadenectomy is critical for staging. Surgical resection is guided by anatomical details and lymph node dissection. Metastatic and unresectable gastric cancer treatment includes cytotoxic agents like fluoropyrimidines, platinum, taxanes, and irinotecan. Combination regimens offer better outcomes. Immunotherapy, including PD-1 inhibitors, is effective in MSI-H and PD-L1-positive tumors. The KEYNOTE-158 trial approved pembrolizumab for MSI-H/dMMR tumors. The KEYNOTE-061 trial showed pembrolizumab's efficacy in PD-L1-positive patients. HER2-positive gastric cancer is treated with trastuzumab, with the ToGA trial establishing its role. New agents like trastuzumab deruxtecan show promise. Antiangiogenic therapy with ramucirumab and combination with immunotherapy is explored. Investigational biomarkers like EGFR and Claudin 18.2 are under study. Liquid biopsy