Background: Omega-3 polyunsaturated fatty acids may modulate lipid-mediated inflammatory pathways implicated in migraine, yet pediatric trial methodologies evaluating biologic target engagement remain limited. This study evaluated the feasibility of conducting a pediatric nutrition-based migraine intervention trial integrating longitudinal dried blood spot biomarker collection, validated patient-reported outcome measures, dietary assessment, and caregiver-reported acceptability measures. Methods: A quasi-randomized, double-blind, placebo-controlled feasibility trial was conducted at two academic pediatric neurology clinics. Children and adolescents aged 10-17 years with migraine were assigned 1:1 using sequential alternating allocation to daily omega-3 supplementation (850 mg eicosapentaenoic acid + docosahexaenoic acid) or matched coconut oil placebo for 12 weeks. Feasibility outcomes included recruitment yield, participant retention, caregiver-reported supplement adherence, dried blood spot biospecimen completion, 24-hour dietary recall completion, and intervention acceptability assessed via caregiver exit questionnaire. Feasibility benchmarks were established post hoc based on published pediatric trial literature: recruitment >70% of target sample, retention [≥]70%, supplement adherence [≥]70% of caregivers reporting administration on most days, biospecimen completion [≥]90%, dietary recall completion [≥]80%, and acceptability rated favorably by [≥]70% of caregivers. Clinical efficacy outcomes will be reported separately. Results: Of 58 individuals assessed for eligibility, 57 were enrolled and allocated (29 intervention, 28 placebo). Forty-four participants (77%) completed the 12-week follow-up (22 per group), meeting the retention benchmark. Dried blood spot collection was completed at both time points for all participants who attended study visits (100%). All 44 study completers finished all four planned dietary recalls (100% completion). Caregiver-reported acceptability was high, with the majority rating daily supplement administration as acceptable and reporting openness to future dietary supplement use for migraine management. Thirteen participants discontinued: five withdrew, five were lost to follow-up, two discontinued due to supplement palatability, and one no longer met inclusion criteria. Structured telephone follow-up at weeks 4 and 8 supported retention and adherence monitoring. Conclusions: This feasibility trial demonstrated that a pediatric nutrition-based migraine intervention integrating dried blood spot biomarker collection, repeated dietary recalls, validated patient-reported outcomes, and structured remote follow-up is feasible and acceptable to families. All six post-hoc feasibility benchmarks were met. Findings support progression to a larger-scale randomized controlled trial with modifications including concealed randomization, prospective daily headache diaries, and longer intervention duration. Trial registration: ClinicalTrials.gov, NCT06899074. Registered 20 March 2025.