Adherence to pediatric atopic dermatitis (AD) treatment regimens can be complex and a major challenge to optimizing treatment outcome. We aimed to review factors associated with nonadherence in pediatric AD and propose interventions to improve adherence. PubMed and EMBASE databases were systematically searched for articles from 2000 to February 2023 related to AD and adherence, with an additional update in December 2023. Non-human studies, reviews, commentaries, and meta-analyses were excluded. Articles were sorted into pediatric versus adult study population based on volume. Herein, we examine the results of papers discussing adherence factors related to pediatric patients. A total of 62 studies met inclusion criteria. Thirty-six studies surveyed patients and caregivers (N = 10,268) to identify barriers to treatment adherence. None of the included studies were specific to systemic medications. Barriers includedpoor caregiver quality of life, inadequate AD-related education, topical corticosteroid (TCS) phobia, unclear therapy-related instructions, and dissatisfaction with physician interaction. Five studies solely measured adherence using medication electronic monitoring systems, Morisky medication adherence scale, or self-reported adherence to measure adherencetotopical medications. Twenty-one studies described interventions involving nurse-led or web-based education programs, text message or email reminders, and TCS education. Adherence was improved with caregiver education programs, daily text-message reminders, eczema action plans, TCS potency "traffic light" color system, and frequent follow-up visits. Adherence to pediatric AD treatment poses a multifactorial challenge for caregivers and patients. This study provides an index of strategies to optimize adherence, as it is essential for prevention of long-term sequela associated with AD in children. As the AD treatment landscape rapidly expands, further studies are vital to assess pediatric adherence to new topical, oral, and injectable medications. PROSPERO: CRD42023488557.