The current review aimed to systematically describe and synthesize health outcomes and factors associated with health literacy and physical frailty among older adults. Seven electronic databases were searched for observational studies published in English, from database inception to March 31, 2021. The study protocol was registered with PROSPERO. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale. Among the 479 studies identified, nine (6,337 participants) met eligibility criteria. Common factors associated with health literacy and physical frailty were lower educational level, multiple comorbidities, and cognitive dysfunction. Health literacy was mainly associated with self-reported outcomes, whereas physical frailty was related to clinical outcomes. Prospective studies are required to identify the impact of limited health literacy, combined with frailty, on long-term health outcomes in older adults. Health literacy interventions should consider the older adult population with multiple comorbidities. [Research in Gerontological Nursing, 15(1), 39-52.].