Poorly controlled postoperative pain remains a significant healthcare issue, affecting over 80% of patients in the US. Despite advancements in pain management, inadequate control of acute postoperative pain is linked to increased morbidity, functional impairment, delayed recovery, prolonged opioid use, and higher healthcare costs. It also predicts the development of chronic pain. Effective analgesic strategies are needed to prevent this progression. While conventional opioids are standard, they carry risks of adverse events, limiting optimal dosing. Newer opioids, such as oliceridine, selectively modulate μ-receptor activity, offering improved safety and efficacy. Local anesthetics and nonopioid analgesics show potential as preventive interventions, though results are inconsistent. Multimodal analgesia, combining various agents, is widely accepted for reducing acute postoperative pain and opioid use. However, more research is needed to confirm its effectiveness in preventing chronic pain. Newer selective μ-opioid agonists, like PZM21 and oliceridine, offer a wider therapeutic window, potentially improving pain control with fewer side effects. Despite these advances, inadequate pain relief continues to negatively impact patient outcomes, emphasizing the need for better management strategies.Poorly controlled postoperative pain remains a significant healthcare issue, affecting over 80% of patients in the US. Despite advancements in pain management, inadequate control of acute postoperative pain is linked to increased morbidity, functional impairment, delayed recovery, prolonged opioid use, and higher healthcare costs. It also predicts the development of chronic pain. Effective analgesic strategies are needed to prevent this progression. While conventional opioids are standard, they carry risks of adverse events, limiting optimal dosing. Newer opioids, such as oliceridine, selectively modulate μ-receptor activity, offering improved safety and efficacy. Local anesthetics and nonopioid analgesics show potential as preventive interventions, though results are inconsistent. Multimodal analgesia, combining various agents, is widely accepted for reducing acute postoperative pain and opioid use. However, more research is needed to confirm its effectiveness in preventing chronic pain. Newer selective μ-opioid agonists, like PZM21 and oliceridine, offer a wider therapeutic window, potentially improving pain control with fewer side effects. Despite these advances, inadequate pain relief continues to negatively impact patient outcomes, emphasizing the need for better management strategies.