Background and Objectives: The perioperative period is characterized by marked biological stress responses that extend beyond direct tissue injury. Innate immune activation during surgery is largely driven by molecular danger signals. Surgical trauma, ischemia–reperfusion injury, blood transfusions, mechanical ventilation, and perioperative infections are critical events that result in the release of danger signals: damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). This narrative review examines perioperative DAMP and PAMP sources, their molecular recognition pathways, and their clinical and oncological significance. Materials and Methods: A literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science databases for English-language articles published up to July 2026. Search terms included DAMPs, PAMPs, perioperative, surgical stress, cancer surgery, innate immunity, PRRs, TLRs, inflammasome, HMGB1, mtDNA, perioperative immunosuppression, and anesthesia. Results: Danger signals interact with pattern-recognition receptors, including Toll-like receptors and inflammasome pathways, driving sterile inflammation, immune dysregulation, and postoperative organ injury. Rather than initiating these cascades, anesthetics and opioids act as modulators. In cancer surgery, heightened danger signaling and temporary immunosuppression may compromise host defenses during a vulnerable window. Conclusions: Circulating DAMPs and potentially selected PAMP-related markers warrant further investigation as biomarkers for perioperative risk stratification. Overcoming translational barriers will require standardized assays, validation of biomarker signatures, and integration of artificial intelligence-driven molecular profiling to advance personalized onco-anesthesia strategies.

Opioids represent one of the oldest classes of drugs in medicine and remain central to pain management to this day. However, their use is limited by a series of adverse effects, and they are notorious for their addiction potential and for contributing to the opioid epidemic in the US. Nanomedicine, the branch of nanotechnology that utilizes materials at the nanoscale for drug delivery, provides a unique platform that can potentially revolutionize conventional opioid treatment. The aim of this literature review is to summarize the latest research on opioid nanoformulations and their potential to increase analgesic efficacy while minimizing associated risks. Preclinical studies have already demonstrated that both liposomal and dendrimer-based opioid formulations allow for extended release and, consequently, more prolonged and stable analgesia. Moreover, nanoemulsions are currently being investigated for the delivery of opioid compounds, offering formulation versatility and improved bioavailability while maintaining an improved safety profile. At the same time, the use of nanomedicine for vaccines against opioids may enable novel therapeutic strategies to be developed for individuals with opioid addiction. However, several barriers need to be overcome for the promise of nanomedicine to be fulfilled, including the lack of clinical trials, difficulties in mass production of several nanoparticles, toxicity concerns, and regulatory issues.