A male patient in his 60s was admitted due to unexplained neutrophilic leucocytosis. Further diagnostic workup revealed a large gastric polyp with partial pyloric obstruction. Biopsy revealed numerous neutrophils surrounding atypical cells resembling Reed-Sternberg cells. The diagnosis of gastric Hodgkin's lymphoma was confirmed through immunohistochemistry. According to his disease stage and high cardiac risk, he was started on the GVP (gemcitabine, vinorelbine and prednisone) protocol. Following a partial response, he experienced disease progression and relapse with hepatic involvement, indicating relapsed and refractory disease. Therefore, he was started on nivolumab, which was the most suitable option, given his specific tumour microenvironment. In the light of this, we recommend a deeper understanding of the tumour microenvironment for each patient to guide effective treatment strategies. This is especially important in the era of advanced immunotherapies, such as programmed death-1 and programmed death-ligand 1 inhibitors and chimeric antigen receptor T-cell therapy.