The present study addressed an area of research not yet sufficiently investigated: the environmental sensitivity trait in relation to perceived marginalization in the classroom, dropout intentions, and the quality of teacher-student relationship. Adopting a psychosocial perspective and based on a single study survey with a group of Italian secondary school students, we applied a moderated mediation model. The aim was to determine whether environmental sensitivity was indirectly related to students' dropout intentions via perceived classroom marginality. Specifically, we proposed that the quality of the teacher-student relationship could act as a protective factor for the well-being of highly sensitive students and, therefore, moderate the relationships between environmental sensitivity and both marginality and dropout intentions. Our research findings partially confirmed these initial hypotheses. An indirect relationship between environmental sensitivity and dropout intentions through marginality was only found when the quality of the teacher-student relationship was low. These findings suggest that positive teacher-student relationship can have a buffering effect, reducing the risk of marginalization for highly sensitive students and thus potentially reducing the risk of early school leaving. Conversely, teacher-student relationship did not moderate the relationship between environmental sensitivity and dropout intentions. Considering these findings, we discuss implications for emerging school-based research on environmental sensitivity and offer insights into potential interventions to enhance highly sensitive students' well-being and academic trajectories.