Background Pancreatic adenocarcinoma with liver metastases (PCLM) has a poor prognosis with a median survival of ≤6-months. Treatment options are limited as only a few patients can undergo curative surgery, therefore locoregional therapies such as liver-directed therapy (LDT) may offer an adjunct to systemic therapies. The purpose of this retrospective study is to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with Yttrium-90 (Y90), trans-arterial chemoembolization (TACE), and radiofrequency ablation (RFA) with systemic chemotherapy in the treatment of PCLM. Methods We retrospectively evaluated 42 patients, with data available on 39 patients, with PCLM who underwent LDT between February 2007 and March 2019. Patient outcomes were assessed using response evaluation criteria in solid tumors (RECIST), Version 1.1 treatment-related adverse events were assessed using common terminology criteria for adverse events (CTCAE), version 5.0. Results Of 39 patients, 56% underwent TARE, 36% RFA, and 7.8% TACE. The median overall survival (mOS) was 5-months (range 4 to 5.5-months) from the application of LDT and the one-year mOS was 7.8-months (6.5 to 9.5-months). Overall and liver-specific disease response included complete response in 2.5%, partial response in 59%, stable disease in 21%, and progression of disease in 18% of patients. Grade 3 toxicities included abdominal pain in 13%, hyperbilirubinemia in 7.7%, fever in 7.7%, abscess in 2.6%, and thrombocytopenia in 5.1% of patients. Conclusion LDT can be safely combined with systemic chemotherapy for the treatment of PCLM. LDT may be the treatment opportunity for PCLM. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.