Inclusion criteria: * Histologically or cytologically confirmed diagnosis of gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or advanced, unresectable, or metastatic esophageal adenocarcinoma. * Disease measurable according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1), as assessed by the local investigator/radiologist. Lesions located in a previously irradiated area are considered measurable if progression in those lesions has been demonstrated. * Has received, and progressed with, at least two previous regimens of chemotherapy and/or immunotherapy for advanced, unresectable, or metastatic gastroesophageal adenocarcinoma. * Participants are eligible regardless of human epidermal growth factor receptor 2 (HER2) status. Participants who are HER2+ must have previously received trastuzumab when available/appropriate * Have adequate organ function * Have provided a tumor tissue sample for trophoblast cell surface antigen 2 (TROP2) status determination by the central laboratory prior to randomization for stratification * Participants who have AD due to prior cancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrinology-related AD who are receiving appropriate treatment with hormone replacement therapy are eligible. * Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as assessed by the local site investigator/radiologist. * Has an Eastern Cooperative Oncology Group (ECOG) functional status of 0 or 1 within 3 days prior to randomization. * Has the ability to swallow oral medications for those who can receive trifluridine-tipiracil. * Participants infected with the human immunodeficiency virus (HIV) must have their HIV well controlled on antiretroviral therapy (ART). * Participants who are positive for hepatitis B surface antigen (HBsAg) are eligible if they have received antiviral therapy for hepatitis B virus (HBV) and have an undetectable HBV viral load. * Participants with a history of hepatitis C virus (HCV) infection are eligible if their HCV viral load is undetectable. Exclusion criteria: * Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing * Has grade ≥2 peripheral neuropathy * Has active inflammatory bowel disease requiring immunosuppressive medication or a history of inflammatory bowel disease (e.g. e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea) * Has significant uncontrolled cardiovascular or cerebrovascular disease, including New York Heart Association class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of the corrected QT interval (QTcF) to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to the first dose of the study intervention * Has pleural, ascitic, or pericardial fluid accumulation requiring drainage or diuretic medications within 2 weeks prior to the first dose of the study intervention * Has received prior treatment with a trophoblast antigen 2 (TROP2) antibody-drug conjugate (ADC), a topoisomerase 1 inhibitor, and/or topoisomerase 1 inhibitor-based chemotherapy. * Has received prior systemic anticancer therapy within 2 weeks prior to the first dose of the study intervention * Has received prior radiotherapy within 2 weeks prior to the first dose of the study intervention, has radiation-related toxicities requiring corticosteroids and/or has had radiation pneumonitis * Has received a live or live attenuated vaccine within 30 days prior to the first dose of the study intervention * Is currently receiving a potent and/or moderate inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of treatment with the study intervention. The washout period required before starting the study intervention is 2 weeks. * You have received an investigational agent or used an investigational device within 4 weeks prior to the first dose of the study intervention. * Has an additional known malignancy that is progressing or has required active treatment within the past 3 years. * Has known active metastases in the central nervous system (CNS) and/or carcinomatous meningitis. * He has an active infection that requires systemic therapy. * HIV-infected participants with a history of Kaposi's sarcoma and/or multicentric Castleman disease. * Has concurrent active hepatitis B (defined as positive hepatitis B surface antigen (HBsAg) and/or detectable HBV deoxyribonucleic acid (DNA)) and hepatitis C virus (HCV) infection defined as positive anti-HCV antibody (Ab) and detectable HCV ribonucleic acid (RNA). * You have had major surgery or a significant traumatic injury within the 4 weeks prior to the first dose of the study intervention. The expectation of needing major surgery during the course of treatment with the study intervention is also exclusionary. * Has severe hypersensitivity (grades >=3) to sacituzumab tirumotecan (MK-2870), to any of its excipients or to another biological therapy. * Has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) requiring steroids or has current pneumonitis/ILD and/or has had radiation pneumonitis * Has received a live or live attenuated vaccine within 30 days prior to the first dose of the study intervention * Is currently receiving a potent and/or moderate inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of treatment with the study intervention. The washout period required before starting the study intervention is 2 weeks. * You have received an investigational agent or used an investigational device within 4 weeks prior to the first dose of the study intervention. * Has an additional known malignancy that is progressing or has required active treatment within the past 3 years. * Has known active metastases in the central nervous system (CNS) and/or carcinomatous meningitis. * He has an active infection that requires systemic therapy. * HIV-infected participants with a history of Kaposi's sarcoma and/or multicentric Castleman disease. * Has concurrent active hepatitis B (defined as positive hepatitis B surface antigen (HBsAg) and/or detectable HBV deoxyribonucleic acid (DNA)) and hepatitis C virus (HCV) infection defined as positive anti-HCV antibody (Ab) and detectable HCV ribonucleic acid (RNA). * You have had major surgery or a significant traumatic injury within the 4 weeks prior to the first dose of the study intervention. The expectation of needing major surgery during the course of treatment with the study intervention is also exclusionary. * Has severe hypersensitivity (grades >=3) to sacituzumab tirumotecan (MK-2870), to any of its excipients or to another biological therapy. * Has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) requiring steroids or has current pneumonitis/ILD and/or has had radiation pneumonitis * Has received a live or live attenuated vaccine within 30 days prior to the first dose of the study intervention * Is currently receiving a potent and/or moderate inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of treatment with the study intervention. The washout period required before starting the study intervention is 2 weeks. * You have received an investigational agent or used an investigational device within 4 weeks prior to the first dose of the study intervention. * Has an additional known malignancy that is progressing or has required active treatment within the past 3 years. * Has known active metastases in the central nervous system (CNS) and/or carcinomatous meningitis. * He has an active infection that requires systemic therapy. * HIV-infected participants with a history of Kaposi's sarcoma and/or multicentric Castleman disease. * Has concurrent active hepatitis B (defined as positive hepatitis B surface antigen (HBsAg) and/or detectable HBV deoxyribonucleic acid (DNA)) and hepatitis C virus (HCV) infection defined as positive anti-HCV antibody (Ab) and detectable HCV ribonucleic acid (RNA). * You have had major surgery or a significant traumatic injury within the 4 weeks prior to the first dose of the study intervention. The expectation of needing major surgery during the course of treatment with the study intervention is also exclusionary. * Has severe hypersensitivity (grades >=3) to sacituzumab tirumotecan (MK-2870), to any of its excipients or to another biological therapy. * Has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD and/or is on other biological therapy. * Has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD and/or is on other biological therapy. * Has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.