Background <p>Osteosarcopenia, characterized by muscle loss and osteoporosis, has emerged as a prognostic marker for various malignancies. However, its impact on the immune response in gastric cancer remains unclear. This study aimed to assess the clinical significance of osteosarcopenia and its relationship with the immune microenvironment in patients with advanced gastric cancer.</p> Methods <p>This study included 105 patients with pathological stage II/III gastric cancer who underwent gastrectomy between 2018 and 2022. Preoperative computed tomography was used to measure muscle mass and bone density, with sarcopenia and osteoporosis defined as values below the respective standard thresholds. Sarcopenia and osteoporosis were identified when both conditions were present. We explored the relationships between osteosarcopenia, clinicopathological factors, and prognoses. Additionally, immune marker expression was evaluated via immunohistochemistry.</p> Results <p>Among the 105 patients, 37 (35%) were diagnosed with osteosarcopenia. This condition significantly correlated with performance status, body mass index, and disease recurrence (all <i>p</i> &lt; 0.05). Overall survival and relapse-free survival were significantly lower in the osteosarcopenia group than those in the non-osteosarcopenia group (all <i>p</i> &lt; 0.05). Moreover, the osteosarcopenia group had significantly fewer CD8-positive, programmed cell death protein 1-positive, and programmed death-ligand 1-positive cells than that of the control group (all <i>p</i> &lt; 0.05).</p> Conclusions <p>Our findings suggest that osteosarcopenia is associated with the tumor microenvironment and might serve as a prognostic indicator in patients with advanced gastric cancer.</p>