Given extensive pertinent disease factors and evolving medical treatments, this systematic review explores qualitative and quantitative cystic fibrosis (CF) research surrounding self‐concept, an overarching perception of self. Research methodologies, self‐concept dimensions, prominent self‐concept findings and clinical recommendations are identified. Preferred Reporting Items for Systematic Review and Meta‐analyses guidelines were applied. PubMed, Scopus, Medline, Psycinfo, CINAHL (ebsco), and CENTRAL Cochrane electronic databases were searched from 2012 to 2022. Methodological quality was assessed using the critical appraisal skills program. Data‐based convergent synthesis was applied to analyze and report on qualitative and quantitative studies in parallel. Thirty‐seven publications met the inclusion criteria, most of which employed a cross‐sectional, single‐center design within an adolescent and adult population. Self‐efficacy, self‐esteem, and self‐identity studies were dimensions of self‐concept identified, with studies relating to self‐efficacy surrounding physical health management most prevalent. All three dimensions were positively associated with improved treatment adherence and psychosocial health. Efficacy tested intervention programs to enhance self‐concept are limited; however, an extensive range of clinical recommendations are offered, highlighting the importance of clinician self‐concept awareness, quality clinician–patient conversations and online CF peer‐support. Self‐concept is an important mechanism to optimize patient outcomes. Further CF self‐concept research is required, particularly multicenter, longitudinal, and interventional studies. Early childhood, post lung transplant and the older adult CF population in particular, lack research attention. Given the potential impact of rapidly evolving CF transmembrane conductance regulator modulator drugs on many aspects of self, future self‐concept research beyond the dimension of self‐efficacy may be beneficial.