Background Based on previous reports of disparities in financial burden following cancer, this study aims to characterize mechanisms of disparities experienced by caregivers of children with cancer, including the impact of work flexibility and social support. Methods Cross-sectional survey (in English or Spanish) of caregivers of children with cancer that assessed household material hardship (HMH), financial toxicity and income change. Results Of 156 caregivers surveyed, 32% were Hispanic and 32% were low income. Hispanic caregivers were more likely to report HMH and financial toxicity compared to non-Hispanic White and Asian (HMH 57% v. 21% v. 19%, p<0.001; financial toxicity 73% v. 52% v. 53%, p=0.07). Low and middle income caregivers were more likely to experience HMH and financial toxicity compared to high income (HMH: 68% low v. 38% middle v 8.7% high, p<0.001; financial toxicity: 81% v. 68% v. 44%, p<0.001). All income categories demonstrated significant increases in HMH one year after diagnosis. Seventeen percent reported >40% income loss, more of whom were low income than high income (27% v. 12%, p=0.20). Work flexibility and social support were associated with income and financial toxicity. Conclusion HMH, financial toxicity, and income loss are prevalent after a child’s cancer diagnosis, suggesting that screening should be incorporated into routine care. This financial burden disproportionately affects low income and Hispanic caregivers. Further research is underway to understand how safety net services are utilized by families, how best to support families with HMH, and how the financial burden of cancer has been impacted by COVID-19.