Depression is a common comorbidity in gastric cancer (GC) patients, with prevalence rates reaching up to 57%, particularly in advanced stages and during active treatment. While prior studies have explored the bidirectional relationship between GC and depression, this editorial provides a structured synthesis of therapeutic strategies including pharmacological, psychotherapeutic, integrative, and biomarker-driven interventions, within a multidisciplinary care framework. Depression may exacerbate tumor progression through chronic stress and neurotransmitter dysregulation, such as β2-adrenergic receptor activation, while the cancer burden deepens psychological distress. Antidepressants, especially selective serotonin reuptake inhibitors, have demonstrated efficacy in alleviating depressive symptoms in up to 70% of cases, particularly when used alongside chemotherapy. Psychotherapeutic modalities, including cognitive-behavioral therapy and family-based interventions, help reduce depressive symptoms, improve coping mechanisms, and prevent relapse. Integrative strategies like music therapy, mindfulness, and physical activity further support emotional well-being, particularly in mild-to-moderate depression. Multidisciplinary care that combines nutritional support, pain control, and psychosocial interventions is essential. Notably, the integration of interventional therapies with traditional Chinese medicine has shown potential in stabilizing tumor growth and improving mental health, enabling functional "tumor-bearing survival". Emerging immunotherapies such as cadonilimab may also contribute indirectly to depression alleviation by enhancing treatment efficacy and extending survival. Future research should focus on biomarker-guided approaches, such as targeting β2-adrenergic signaling, and developing personalized psychosocial care models. A holistic approach that integrates both physical and psychological care is vital to improving outcomes and quality of life in GC patients.