Aims and objectives: To identify factors associated with the caregiving appraisal of informal caregivers. Background: Caregiving appraisal, the cognitive evaluation of the caregiving situation, is an essential factor in determining positive or negative caregiving outcomes. Identifying factors associated with appraisal is fundamental for designing effective health promotion strategies. Design: A systematic review. Methods: PubMed, EMBASE, CINAHL, PsycINFO, Social Sciences Citation Index, Scopus, CNKI and Wanfang Database were searched for papers published from 1984 to December 2018. Keywords related to informal caregivers' caregiving appraisal were used. Cross-sectional and cohort studies were included. The Quality Assessment and Validity Tool for Correlational Studies, and the CASP Cohort Study Checklist were used for quality assessment. Descriptive and narrative synthesis were used to analyse data. Social ecological model was used for classifying the associated factors into different levels. The PRISMA checklist was followed. Results: Forty studies were included. The quality of the studies was moderate to high. Data were organised into three levels (individual, interpersonal and community level) and categorised into modifiable factors (e.g. patient behavioural problems, caregiver self-efficacy and social support) and nonmodifiable factors (e.g. caregiving duration, gender and education). The majority of studies have investigated the factors at the individual level. Conclusion: There are inconsistencies in the understanding of caregiving appraisal, and consensus is needed for conceptual clarity. Caregiving appraisal is associated with three levels of factors. These modifiable factors provide evidence for designing evidence-based interventions, and the nonmodifiable factors help identify confounding factors in assessment and appraisal. Relevance to clinical practice: Nurses are the best-placed healthcare professionals to support informal caregivers. The three levels of associated factors and the interactive approaches provide direction for informing clinical nursing practice. They also provide evidence for healthcare researchers and policymakers to develop interventions and theoretical perspectives and to better allocate healthcare resources.