Background: Clinical trial (ClTr) participation is associated with improved childhood cancer outcomes, but significant socioeconomic and sociodemographic disparities in trial enrollment exist. Identifying modifiable barriers to participation such as household material hardship (HMH) and limited health literacy (HL), is essential to improving ClTr access. We compared differences in caregiver-reported barriers to pediatric oncology ClTr participation across socioeconomic status (SES) and racial/ethnic groups through a nationwide anonymous online survey of caregivers of children with cancer. We also explored associations between caregiver HL, HMH, and barriers to trial participation. Procedures: English- and/or Spanish-speaking caregivers of children diagnosed with cancer in the last 5 years completed the Research Participation Survey – Caregiver (RPS-C) to assess barriers to ClTr participation, the validated Health Literacy Survey-12 (HLS 19-Q12) health literacy assessment, and the WellRx questionnaire measuring HMH. Results: Of the 59 participants, 64% were socioeconomically under-resourced, 52.5% identified as racially/ethnically underrepresented, and 62% reported their child had not participated in a ClTr. Under-resourced caregivers reported higher RPS-C barrier scores than adequately resourced caregivers ( z=3.18, p=0.001). There were no significant differences in barrier scores across underrepresented vs represented racial/ethnic groups ( p=0.203). Lower HL (ρ=˗0.557, p<0.001 ) and higher HMH (ρ = 0.562, p = 0.006) were associated with higher barrier scores. The most frequently identified barrier was difficulty understanding study risks (>90%). Conclusions: Under-resourced SES, HMH, and lower HL were associated with increased barriers to ClTr participation. Caregivers described modifiable barriers that could be targets for intervention to improve ClTr participation and reduce disparities in childhood cancer outcomes.