Chronic postsurgical pain (CPSP) is described as postsurgical pain having a duration of ≥3 months, having variable prevalence in pediatric surgical populations, with an overall prevalence of 20% for 12 months. Children having scoliosis correction and limb amputations have been most studied, respectively, in the non-oncological and oncological populations, in the context of CPSP. For understanding the transition of postsurgical pain from an acute to a chronic state in children, a conceptual biopsychosocial pain model has been proposed. It consists of sensory components, psychological components, behavioral components, and social components. Factors affecting these components are categorized into premorbid injury and recovery, biological factors, and psychosocial factors. The only identified associations with higher risk of CPSP in the non-oncological pediatric population are presurgical pain intensity, child’s anxiety, child’s pain coping efficacy, and parental pain catastrophizing. Perioperative pharmacological interventions can be conceptually aimed at addressing several major contributing factors to CPSP: (1) preexistent pain, either tumor related or chemotherapy related; (2) surgery-related pain, intraoperatively and immediately postoperatively; (3) perioperative anxiety; and (4) opioid-related hyperalgesia. Medications with anxiolytic effects, perioperative-guided imagery, play therapy, and music therapy can be used to reduce perioperative anxiety in children. Perioperative pain can be treated with standard “layered” nonopioid and opioid medications that are well-known for managing nociceptive acute pain, in addition to pain medications known as “modulators/adjuvants” and “anti-hyperalgesic interventions,” with the goal of reducing the magnitude of opioid exposure immediately postoperatively, neuropathic pain, and opioid-induced hyperalgesia.