BACKGROUND Transgender, nonbinary, and gender-diverse (TNG) youth encounter barriers to psychosocial wellness and also describe exploring identities and communities on the web. Studies of cisgender youth connect increased digital technology use with lower well-being, parent relationships, and body image scores as well as increased loneliness and fear of missing out (FOMO). However, little is known about the psychosocial factors associated with digital technology use among TNG compared with cisgender youth. OBJECTIVE This study aims to examine the associations between psychosocial measures and digital technology use and its importance for cisgender and TNG youth. METHODS We surveyed a nationally representative sample of adolescents (aged 13-18 years) about psychosocial wellness and digital technology use. Psychosocial measures included assessment of well-being, parental relationships, body image, loneliness, and FOMO. Digital media use assessments included the short Problematic and Risky Internet Use Screening Scale-3 and the Adolescent Digital Technology Interactions and Importance (ADTI) scale and subscales. We compared psychosocial measures between gender identity groups. We also compared stratified correlations for psychosocial measures (well-being, parent relationships, body image, loneliness, and FOMO) with ADTI and Problematic and Risky Internet Use Screening Scale-3 scores between gender identity groups. All comparisons were adjusted for age, race, and ethnicity. RESULTS Among 4575 adolescents, 53 (1.16%) self-identified as TNG youth. TNG youth had lower scores for well-being (23.76 vs 26.47; <i>P</i>&lt;.001), parent relationships (19.29 vs 23.32; <i>P</i>&lt;.001), and body image (13.50 vs 17.12; <i>P</i>&lt;.001), and higher scores for loneliness (9.28 vs 6.55; <i>P</i>&lt;.001) and FOMO (27.93 vs 23.89; <i>P=</i>.004), compared with cisgender peers. In a pattern different from that of their cisgender peers, better well-being scores and body image for TNG youth predicted higher problematic internet use (PIU) scores (correlation coefficients of 0.32 vs −0.07; <i>P</i>=.004 and 0.26 vs −0.21; <i>P</i>=.002, respectively). FOMO was a stronger positive predictor of higher ADTI total and subscale scores for cisgender youth compared with TNG youth. CONCLUSIONS Overall, this study supports previously demonstrated disparities in the psychosocial wellness of TNG youth and adds that these disparities include loneliness and FOMO. This study shows prediction of PIU by both higher well-being and better body image, indicating that PIU may not be unilaterally driven by problematic factors among TNG youth. We suggest that this may be because of the specific digital media functions that TNG youth engage with as a disenfranchised population.