Cancer is the leading cause of death by disease in developed countries. Children and adolescents with cancer need surgical interventions (ie, biopsy or major surgery) to diagnose, treat, or palliate their malignancies. Surgery is a period of high vulnerability because it stimulates the release of inflammatory mediators, catecholamines, and angiogenesis activators, which coincides with a period of immunosuppression. Thus, during and after surgery, dormant tumors or micrometastasis (ie, minimal residual disease) can grow and become clinically relevant metastasis. Anesthetics (ie, volatile agents, dexmedetomidine, and ketamine) and analgesics (ie, opioids) may also contribute to the growth of minimal residual disease or disease progression. For instance, volatile anesthetics have been implicated in immunosuppression and direct stimulation of cancer cell survival and proliferation. Contrarily, propofol has shown in vitro anticancer effects. In addition, perioperative blood transfusions are not uncommon in children undergoing cancer surgery. In adults, an association between perioperative blood transfusions and cancer progression has been described for some malignancies. Transfusion-related immunomodulation is one of the mechanisms by which blood transfusions can promote cancer progression. Other mechanisms include inflammation and the infusion of growth factors. In the present review, we discuss different aspects of tumorigenesis, metastasis, angiogenesis, the immune system, and the current studies about the impact of anesthetics, analgesics, and perioperative blood transfusions on pediatric cancer progression.