CONTEXT: Alternative pain management interventions involving caregivers may be valuable adjuncts to conventional pain management interventions. OBJECTIVES: Use systematic review methodology to examine caregiver-facilitated pain management interventions in a hospital setting and whether they improve patient, caregiver, provider, or health system outcomes. METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Scopus databases from inception to April 2020. Original research on caregiver-facilitated pain management interventions in hospitalized settings (i.e., any age) were included and categorized into three caregiver engagement strategies: inform (e.g., pain education), activate (e.g., prompt caregiver action), and collaborate (encourage caregiver's interaction with providers). RESULTS: Of 61 included studies, most investigated premature (n = 27 of 61; 44.3%) and full-term neonates (n = 19 of 61; 31.1%). Interventions were classified as activate (n = 46 of 61; 75.4%), inform-activate-collaborate (n = 6 of 61; 9.8%), inform-activate (n = 5 of 61; 8.2%), activate-collaborate (n = 3 of 61; 4.9%), or inform (n = 1 of 61; 1.6%) caregiver engagement strategies. Interventions that included an activate engagement strategy improved pain outcomes in adults (18-64 years) (e.g., self-reported pain, n = 4 of 5; 80%) and neonates (e.g., crying, n = 32 of 41; 73.0%) but not children or older adults (65 years and older). Caregiver outcomes (e.g., pain knowledge) were improved by inform-activate engagement strategies (n = 3 of 3). Interventions did not improve provider (e.g., satisfaction) or health system (e.g., hospital length of stay) outcomes. Most studies were of low (n = 36 of 61; 59.0%) risk of bias. CONCLUSION: Caregiver-facilitated pain management interventions using an activate engagement strategy may be effective in reducing pain of hospitalized neonates. Caregiver-facilitated pain management interventions improved pain outcomes in most adult studies; however, the number of studies of adults is small warranting caution pending further studies.