Background: Cancer is the second leading cause of death among US children. Among Hispanic/Latino (H/L) childhood cancer patients, social, economic, and cultural barriers increase risk for limited access to cancer care and poor health outcomes. We compared the prevalence of material financial hardship (MFH) and food insecurity over time between H/L and non-H/L White families of childhood cancer patients. We hypothesized H/L families would have higher MFH and food insecurity. Methods: In this prospective observational study, parents/guardians (n = 107) of children with newly diagnosed cancer and receiving treatment at Rady Children’s Hospital San Diego were enrolled from July 2019 to November 2021. Eligible participants included primary caregivers of a child aged 0-17 years who was newly diagnosis with cancer and who were able to write and speak English or Spanish. The primary outcomes of MFH and food insecurity were collected via survey at baseline, 3-, 6-, 12- and 24-months following enrollment. Sociodemographic and clinical characteristics were collected at baseline only. Separate generalized estimating equation models with binomial distribution and exchangeable correlation structure were used to assess the longitudinal associations between H/L ethnicity with MFH and food insecurity, adjusting for sociodemographic covariates. Results: Study participants included 61 H/L (57%) and 46 non-H/L White (43%) parents/guardians. The majority were married (74%), < 45 years old (80%), primarily spoke English at home (74%) and had public insurance (55%). At baseline, MFH was reported by 63% of H/Ls and 38% of non-H/L Whites, while food insecurity was reported by 56% of H/Ls and 44% of non-H/L Whites. In adjusted GEE models, H/Ls experienced a lower, though non-significant, risk of both MFH (adjusted Odds Ratio [ORadj] = 0.85, 95% Confidence Interval [95% CI]:0.39-1.87] and food insecurity (ORadj = 0.58, 95% CI:0.22-1.55) over time, compared to non-H/L Whites. Public insurance was associated with increased risk of MFH (ORadj = 2.71, 95% CI:1.23-5.96] and food insecurity (ORadj = 4.09, 95% CI:1.39, 12.05) over time, compared to private insurance. Conclusions: In this prospective study, self-reported MFH and food security were highly prevalent in the 24 months following baseline, though they did not significantly differ between H/L and non-H/L White parents/caregivers. Public insurance was associated with excess risk of both MFH and food insecurity, over time. Despite no observed differences, it is imperative that larger, prospective studies investigate the long-term patterns of social risks among underserved and underrepresented families of childhood cancer patients, as well as the association between social risk and cancer outcomes.