<p>Social media use among adolescents can have adverse repercussions, especially for those exposed to and engaged with e-cigarette-related content. This study examines factors associated with such exposure and engagement among US adolescents (grades 6–12) using data from the 2023 National Youth Tobacco Survey (NYTS). The NYTS is a nationally representative, cross-sectional, school-based, self-administered web survey conducted from March 9 to June 16, 2023, using a stratified, three-stage cluster sampling design. The analytic sample consisted of adolescents who reported using social media (<i>n</i> = 18,797). Independent variables included sociodemographic characteristics, psychological factors, and current e-cigarette use. The dependent variable—exposure and engagement with e-cigarette-related social media content—was measured using three survey items capturing whether participants had seen, liked/commented, or posted such content. Weighted multivariable multinomial logistic regression analyses were conducted to examine associations between independent and dependent variables. Higher e-cigarette-related exposure was observed among females, high schoolers, Hispanics, those with depression, and current e-cigarette users. Posting pictures/videos of e-cigarette use was more common among adolescents who were older, non-Hispanic (NH)-Black, and current e-cigarette users. Liking, commenting, or sharing e-cigarette-related posts was higher among females, NH-Blacks, Hispanics, sexual minorities, those with depression, and current e-cigarette users. Targeted interventions, including educational campaigns, stricter content regulations, and anti-e-cigarette messaging, are essential to reduce adolescent exposure and engagement with e-cigarette-related content.</p>