Scholarly research on commercial sexual exploitation (CSE) of youth has been impeded due to difficulties in researching hidden and vulnerable populations. Drawing from Agnew’s general strain theory, this study utilized multigroup structural equation modeling to explore similarities and differences in vulnerability to CSE across gender. The strain reactive pathway, linking caregiver strain to youth susceptibility to CSE, was tested with data from 1,354 serious youthful offenders, 8.4% of whom indicated CSE. Findings revealed that caregiver strain, such as arrests and substance use, similarly impacted nurturing of boys and girls. Across both genders, poor nurturing was linked to higher negative psychosocial emotion, running away, and initiating substance use and sexual relationships at earlier ages. For males, negative psychosocial emotion and earlier initiation of sexual relationships were significantly related to CSE. In contrast, vulnerability of females was more strongly linked to earlier substance use.