This paper presents the development and validation of the Transgender Health, Resilience, Inner Well-Being, Vitality, and Empowerment (THRIVE) Scale. It offers insights into the well-being of transgender and gender-diverse (TGD) individuals, by considering their unique experiences and challenges. TGD individuals often experience significant health disparities, including mental health issues, substance abuse, physical health problems, and difficulty with providers knowing about their needs. A comprehensive quality-of-life assessment could aid in identifying contributions to poor quality of life (QOL) and knowing which resources are needed to address this effectively. Assessments attempting to address these challenges often have not been studied adequately and/or have limitations of being for one-time use, surgery-focused, lengthy, emotionally taxing, and not inclusive of non-binary individuals’ specific needs. Validated among a sample of TGD individuals (N = 61), the THRIVE scale displayed good internal consistency reliability (α = 0.87), as well as convergent and divergent validity. It had significant negative correlations with measures of psychological symptoms and identity distress and positive correlations with measures of life satisfaction and well-being. The THRIVE scale represents a critical advancement in assessing the QOL of TGD individuals and could be an effective tool for individualized care, research, and conversation with these populations.