The research examined whether clusters of loneliness and social anxiety could be identified through latent profile analysis in a longitudinal study of 892 Chinese adolescents (47.8% male), on average 12.96 (SD = 0.62) years old. Six clusters were identified: (a) low loneliness and social anxiety, (b) average loneliness and social anxiety, (c) high social anxiety and low loneliness, (d) high loneliness and low social anxiety, (e) moderate loneliness and social anxiety, and (f) high loneliness and social anxiety. Findings indicated that baseline family dysfunction and school-related stress served as risk factors for membership in the clusters representing higher levels of loneliness and social anxiety compared to the low cluster. Controlling for the baseline levels of respective outcomes, 6 clusters were differentially related to subsequent comprehensive mental health outcomes, underscoring the importance of the roles of both the loneliness and social anxiety processes in adolescents' mental health. Furthermore, these findings indicated that the interactions between social anxiety and loneliness within individuals were differentially related to levels of comprehensive mental health outcomes, implying the need for intervention programs to be tailored to the members of the specific clusters. Impact and Implications: The findings indicated that loneliness and social anxiety occurred simultaneously as well as independently within individuals. Therefore, prior to the treatment of loneliness and social anxiety in adolescents, professionals should evaluate whether individuals experience loneliness and social anxiety together or independently to provide appropriate interventions. Findings also suggested that family dysfunction and school-related stress were risk factors for the clusters reflecting high loneliness and social anxiety compared to the low cluster. Thus, fostering both positive family and school climates appears necessary to promote adolescents' comprehensive mental health.