Chronic postsurgical pain (CPSP) results from a cascade of events in the peripheral and central nervous systems following surgery. Several clinical predictors, including the prior pain state, premorbid psychological state (e.g., anxiety, catastrophizing), intraoperative surgical load (establishment of peripheral and central sensitization), and acute postoperative pain management, may contribute to the patient's risk of developing CPSP. However, research on the neurobiological and biobehavioral mechanisms contributing to pediatric CPSP and effective preemptive/treatment strategies are still lacking. Here we evaluate the perisurgical process by identifying key problems and propose potential solutions for the pre-, intra-, and postoperative pain states to both prevent and manage the transition of acute to chronic pain. We propose an eight-step process involving preemptive and preventative analgesia, behavioral interventions, and the use of biomarkers (brain-based, inflammatory, or genetic) to facilitate timely evaluation and treatment of premorbid psychological factors, ongoing surgical pain, and postoperative pain to provide an overall improved outcome. By achieving this, we can begin to establish personalized precision medicine for children and adolescents presenting to surgery and subsequent treatment selection.