The purpose of this study was to use data from the National Longitudinal Transition Study–2 (NLTS2) to (a) conceptually identify and empirically establish student, family, and school constructs; (b) explore the degree to which the constructs can be measured equivalently across disability groups; and (c) examine latent differences (means, variances, and correlations) in the constructs across disability groups. Conceptual analysis of NLTS2 individual survey items yielded 21 student, family, and school constructs, and 16 were empirically supported. Partial strong metric invariance was established across disability groups, and in the latent space, a complex pattern of mean and variance differences across disability groups was found. Disability group moderated the correlational relationships between multiple predictor constructs, suggesting the key role of disability-related characteristics in understanding the experiences of youth with disabilities. Implications for future research and practice are discussed.