Orthopedic surgeries are among the most painful procedures performed, particularly those conducted with curative intent for oncologic disease. Severe acute postoperative pain not only increases immediate morbidity but also raises the risk of developing chronic postsurgical pain (CPSP), which is associated with diminished quality of life. Despite standardized surgical and anesthetic protocols, such as Enhanced Recovery After Surgery (ERAS) pathways, postoperative pain experiences remain highly variable across patients undergoing identical oncologic procedures. This variability is explained by the biopsychosocial model of pain, which posits that biological, psychological, and social domains contribute equally to the pain experience. Preoperative assessment should therefore include characterization of these dimensions to define each patient’s pain phenotype and stratify risk into clinically meaningful clusters. These clusters, when combined with surgical complexity, can guide individualized analgesic protocols and determine the appropriate intensity of preventive perioperative interventions. High-risk patients may benefit from aggressive multimodal strategies that include pharmacologic analgesics, regional and neuraxial anesthesia, as well as cognitive-behavioral or acceptance-based therapies, aiming to reduce central sensitization, prevent the transition to CPSP, and improve overall postoperative patient quality of life.