Propofol as an intravenous anesthetic and isoflurane as an inhalational/volatile anesthetic continue to be an important part of surgical anesthetic interventions worldwide. The impact of these anesthetics on tumor progression, immune modulation, and survival rates of cancer patients has been widely investigated. Although most of the preclinical studies have provided a beneficial effect of propofol over isoflurane or other volatile anesthetics, several investigations have shown contradictory results, which warrant more preclinical and clinical studies. Propofol mostly exhibits antitumor properties, whereas isoflurane being a cost‐effective anesthetic is frequently used. However, isoflurane has been also reported with protumorigenic activity. This review provides an overall perspective on the network of signaling pathways that may modulate several steps of tumor progression from inflammation, immunomodulation, epithelial–mesenchymal transition (EMT) to invasion, metastasis, angiogenesis, and cancer stemness and extracellular vesicles along with chemotherapeutic applications and clinical status of these anesthetics. A clear understanding of the mechanistic viewpoints of these anesthetics may pave the way for more prospective clinical trials with the ultimate goal of obtaining a safe and optimal anesthetic intervention that would prevent cancer recurrence and may influence better postoperative survival.