Purpose: Pediatric cancer is a serious problem and still becomes a global challenge today. Various complex stressors due to diagnosis, disease symptoms, and various side-effects from the treatment that children with cancer undergo will cause problems in the child's psychoneuroimmunological aspects. Psychological interventions designed to modulate the stress response include psychoneuroimmunological markers. Unfortunately, there is little evidence to support the effect of psychological interventions on psychoneuroimmunological markers. This systematic review aims to assess the effectiveness of psychological interventions on psychoneuroimmunological markers in children with cancer and to provide a new integrative model for further research. Methods: This systematic review uses four main databases (Scopus, PubMed, ScienceDirect, and ProQuest). The guideline used Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Selecting articles used the Rayyan application. The quality study was conducted using Joanna Briggs Institute (JBI)'s critical appraisal tools. The data were analyzed using the population, intervention, comparison, outcome, and study design (PICO) Synthesis based on similarities and differences in study characteristics to interpret the results. Results: The search results in this systematic review found 1653 articles, 21 of which matched the predetermined inclusion and exclusion criteria. Most of the designs used were randomized controlled trials (57.1%). Massage therapy was the most common type of psychological intervention (14.2%). Almost half of the studies measured psychological responses (38.0%), and psycho-physiological responses (42.9%), and only a small proportion assessed the effectiveness of psychological interventions on neuroimmunological markers in pediatric cancer. Conclusions We recommend the use of psychological interventions as an additional intervention in managing psychoneuroimmunological markers of pediatric cancer. This study offers a new integrative model demonstrating the interaction between stress and psychological intervention involving neuroendocrine and immune mechanisms. However, future researchers need to test all domains of these new integrative models. This will reveal the complex interactions among these components and understand their relevance to health outcomes.