The operative procedure leads to a complex response from the innate and adaptive immune systems. The surgical stress response at the systemic level causes immunosuppression, while locally, inflammation is triggered by the release of alarmins. Excessive release of alarmins can lead to a dysregulated postoperative inflammatory response, increasing the risk of developing infections, systemic inflammatory response syndrome, and sepsis. Numerous factors can influence the inflammatory response, primarily surgical and anesthetic procedures. The duration of surgery, tissue manipulation, and tissue damage are directly proportional to the intensity of the surgical stress response, which is why minimally invasive surgery is advised whenever possible. Anesthetics and anesthetic techniques are involved in the complex interaction with the perioperative immune response. The immunosuppressive effect of inhalational anesthetics in cases of excessive inflammatory response or ischemia-reperfusion injury can be desirable. However, in immunocompromised and oncological patients, it is necessary to seek ways to mitigate their impact on the immune response through the use of regional anesthesia or propofol. Nonetheless, many authors recommend further research to connect current knowledge with clinical implications. The effects of specific anesthetics and adjuvant drugs, as well as the effects of certain techniques on the immune system in the perioperative period, should be included in the anesthetic decisionmaking process. This paper aims to provide a review of current knowledge on the immunomodulatory effects of surgical and anesthetic procedures and how to modify them to achieve better postoperative outcomes.