Local recurrence and hepatic metastasis are still the major causes of death of patients who have undergone resection for pancreatic cancer. To decrease the incidence of local recurrence, we have proposed and devised several trans-tissue and local delivery systems, all of which could be applied immediately after surgery at the resected sites: (1) System I: a drug-loaded photocured gelatinous tissue-adhesive gel (bioactive substance reservoir) that enables the sustained release of a drug, protein, or gene-encoding adenovirus, (2) System II: an anti-cytokine antibody-fixed photocured gelatinous, tissue-adhesive gel (cytokine barrier) that prevents cytokine permeation into the resected tissue, (3) System III: a gene-modified cell sheet that enables the sustained release of a very costly protein produced by gene-transduced cells and (4) System IV: a percutaneous drug-delivery device that enables continuous drug infusion and easy removal from the body. This review article is a summary of our several years of efforts and attempts, which are composed of integrated disciplines including active biomaterials and genetic- and tissue-engineerings, to overcome the recurrence of pancreatic cancer. Here, we outline our proposed strategies and therapeutic devices/materials and discuss their potential therapeutic effectiveness, promises and challenges in the clinical settings.