Gender dysphoria is distress due to a discrepancy between one's assigned gender and gender identity. Adults who wish to access gender clinics are assessed to ensure they meet the diagnostic criteria for gender dysphoria. Therefore, the definition of gender dysphoria has a significant impact on the lives of individuals who wish to undergo physical gender transition. This systematic review aimed to identify and synthesize all existing qualitative research literature about the lived experience of gender dysphoria in adults. A pre-planned systematic search identified 1491 papers, with 20 of those meeting full inclusion criteria, and a quality assessment of each paper was conducted. Data pertaining to the lived experience of gender dysphoria were extracted from each paper and a meta-ethnographic synthesis was conducted. Four overarching concepts were identified; distress due to dissonance of assigned and experienced gender; interface of assigned gender, gender identity and society; social consequences of gender identity; internal processing of rejection, and transphobia. A key finding was the reciprocal relationship between an individual's feelings about their gender and societal responses to transgender people. Other subthemes contributing to distress were misgendering, mismatch between gender identity and societal expectations, and hypervigilance for transphobia.