Background: Historically, objective response rates (ORR) (CR/CRi + PR) in pediatric phase I oncology trials have been < 10%. With an increased emphasis on targeted treatment approaches, safety profiles and response rates may have changed. We analyzed outcomes of recent phase I pediatric oncology trials. Methods: Peer-reviewed phase I pediatric oncology trials published from 2012 through 2017 were identified through a PubMed search. Selection criteria included a pediatric population (median age ≤ 25 years), diagnosis of cancer (including CNS tumors), and a clear dose-escalation schema. Each publication was evaluated for therapy type (cytotoxic versus targeted, combination vs. single agent), trial design, patient characteristics, toxicity, and response. Results: Of 242 publications identified, 89 articles met the inclusion criteria. 46 (52%) incorporated targeted therapies. Total enrollment was 2187 patients; median age at enrollment/trial was 10 years (range 3-25 years). 1990 patients (91%) were evaluable for toxicity, of whom 256 (12.9%) experienced dose-limiting toxicity (DLT) with 3 study-related deaths (0.15%). Of 1708 patients evaluable for response in 78 trials, 287 (16.8%) demonstrated a response (188 CR, 15 CRi, 84 PR). 31 (40%) of trials had no objective responses. Sixteen trials (21%) had an ORR ≥ 25% (leukemia trials = 9, solid tumor trials = 7), of which 8 were combination cytotoxic trials and 8 were targeted trials, the majority enrolling patients with the relevant target (e.g. CD19-directed therapy for CD19+ disease). Comparison between the 46 targeted trials and the 43 cytotoxic trials demonstrated similar pooled rates of DLT (11.1% vs. 15.4%) and ORR (16.9% vs. 16.7%). Conclusions: Our systematic review of recent pediatric oncology phase I trials demonstrated a higher pooled ORR than rates previously reported without increased toxicity. A subset of trials with substantially higher ORR included combination cytotoxic trials and targeted trials with target specific enrollment, supporting earlier introduction of combinatorial approaches and inclusion of pediatric patients with the relevant target in early phase targeted trials.