The incidence of pancreatic cancer is elevated in patients with systemic lupus erythematosus (SLE), particularly those who have undergone renal transplantation. However, the feasibility of performing a pancreaticoduodenectomy (PD) for this specific patient group remains uncertain. Here, we present a case of a 44-year-old male with SLE and a history of renal transplantation who was newly diagnosed with pancreatic cancer. The patient successfully underwent PD combined with resection and reconstruction of the superior mesenteric vein and had an uneventful post-operative course. In silico analysis revealed higher ratios of naïve B cells, CD8+ T cells, CD4+ memory-activated T cells, and monocytes in the tumor tissue of this patient compared to most patients in The Cancer Genome Atlas and PACA-AU datasets (exceeding the mean + standard error value for each cell type). In addition, the patient exhibited higher proportions of naïve B cells, memory B cells, CD4+ memory-activated T cells, regulatory T cells, resting natural killer cells, and activated dendritic cells in the lymph nodes compared to patients in the GSE103787 dataset (exceeding the mean + standard error value for each cell type). Furthermore, expression levels of cytotoxic marker genes (granzyme B and perforin 1) were higher in both the tumor tissue and lymph nodes compared to public datasets (exceeding the mean + standard error value). In conclusion, this case demonstrates that a patient with SLE and renal transplantation can tolerate PD. In addition, it provides the first description of this patient group’s unique anti-tumor immune microenvironment through in silico analysis.