The purpose of this study is to determine the safety of peri-operative gemcitabine, cisplatin, and pembrolizumab in patients with BTC, as well as whether the combination of gemcitabine, cisplatin, and pembrolizumab (gem/cis/pembro) is feasible and lead to pathologic responses.

Inclusion Criteria:

• Must have a newly diagnosed, biopsy-proven biliary tract cancer (BTC) including gallbladder, intrahepatic, extrahepatic, and hilar cholangiocarcinoma.
• Resectable BTC (biliary tract cancer)
• Measurable disease per RECIST 1.1 as determined by the investigator.
• Age ≥18 years.
• ECOG (Eastern Cooperative Oncology Group) performance status ≤1 or Karnofsky ≥80
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Patients must have adequate liver function defined by study-specified laboratory tests.
• Patients with chronic or acute HBV or HCV infection must have disease controlled prior to enrollment.
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Receiving, or previously received, any systemic chemotherapy, or investigational agent for BTC.
• Has received prior radiotherapy within 2 weeks of start of study intervention.
• Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.
• Have been diagnosed with another cancer or myeloproliferative disorder whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this study's investigational drugs.
• Has a known history of Human Immunodeficiency Virus (HIV)/AIDS
• Has active co-infection with HBV and HDV.
• Has a diagnosis of immunodeficiency.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Systemic or topical corticosteroids at immunosuppressive doses.
• Prior allogeneic stem cell transplantation or organ transplantation.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation, including corneal transplants.
• Uncontrolled intercurrent active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Evidence of clinical ascites.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Previously identified allergy or hypersensitivity to monoclonal antibodies or any component of the study treatment formulations.
• Pregnant or breastfeeding.
• WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
• Subjects unable to undergo venipuncture and/or tolerate venous access.
• Patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).