Abstract Background and Objectives When staff experience responsive behaviors from residents, this can lead to decreased quality of work life and lower quality of care in long-term care homes. We synthesized research on factors associated with resident responsive behaviors directed toward care staff and characteristics of interventions to reduce the behaviors. Research Design and Methods We conducted a mixed-methods systematic review with quantitative and qualitative research. We searched 12 bibliographic databases and “gray” literature, using 2 keywords (long-term care, responsive behaviors) and their synonyms. Pairs of reviewers independently completed screening, data extraction, and risk of bias assessment. We developed a coding scheme using the ecological model as an organizing structure and prepared narrative summaries for each factor. Results From 86 included studies (57 quantitative, 28 qualitative, 1 mixed methods), multiple factors emerged, such as staff training background (individual level), staff approaches to care (interpersonal level), leadership and staffing resources (institutional level), and racism and patriarchy (societal level). Quantitative and qualitative results each provided key insights, such as qualitative results pertaining to leadership responses to reports of behaviors, and quantitative findings on the impact of staff approaches to care on behaviors. Effects of interventions (n = 14) to reduce the behaviors were inconclusive. Discussion and Implications We identified the need for an enhanced understanding of the interrelationships among factors associated with resident responsive behaviors toward staff and processes leading to the behaviors. To address these gaps and to inform theory-based effective interventions for preventing or mitigating responsive behaviors, we suggest intervention studies with systematic process evaluations.