Introduction. Increased life expectancy leads to consequent long-term care needs, where informal caregivers may experience overload and strain associated with caregiving, influencing the well-being and health of individuals and eventually leading to an effort to fulfill their role. Within this context, a condition called caregiver role strain has been identified. Objective. To investigate the clinical indicators of the nursing diagnosis caregiver role strain as described in the literature. Materials and Methods. This study is a systematic review of diagnostic accuracy conducted in October 2023, following the recommendations of the Joanna Briggs Institute. The review protocol was registered and approved in the Prospective International Register of Systematic Reviews under registration number CRD42022377411. The QUADAS-2 tool was used to assess the risk of bias and quality of the studies. The databases included SciVerse Scopus (Elsevier), MEDLINE/PubMed (via National Library of Medicine), Latin American and Caribbean Health Sciences Literature (LILACS), CINAHL with Full Text (EBSCO), and PsycINFO (APA), with 48 articles included for quantitative synthesis. Results. Fourteen defining characteristics were identified from the literature, with a predominance of the following indicators: depressive symptoms (45.8%), anxiety (41.6%), physical decline (31.2%), fatigue (22.9%), disturbed sleep pattern (20.8%), emotional disturbance, and irritability (16.6%). The findings suggest that, within the defined circumstances and limitations of the study, examining defining characteristics for the diagnosis caregiver role strain holds potential for advancing scientific knowledge regarding human responses to the challenges experienced by caregivers. Evidence for Practice. The study aligns with clinically relevant indicators crucial for refining and updating the diagnosis, thereby enhancing its level of evidence and clinical accuracy. Simultaneously, it supports addressing the gap in caregiver support and standardized nursing care plans.