Introduction: Oncology has transformed with the use of immunotherapy to detect and destroy tumor cells using the body's immune system. Nevertheless, there are several challenges that monotherapies have, including tumor heterogeneity, immune resistance, and poor response rates. Combination immunotherapy has thus become a good option in order to increase therapeutic efficacy and overcome these barriers. Methods: The present literature review examined articles published in the period between 2020 and 2025 in PubMed, ScienceDirect, and Google Scholar. The data collection and synthesis of key preclinical and clinical data were guided using strategic keywords such as combination immunotherapy, checkpoint inhibitors, tumor heterogeneity, and oncolytic viruses. Results: The results indicate that the combined immunotherapies (including dual checkpoint inhibitors, immunotherapy combined with chemotherapy, radiotherapy, or targeted therapy) result in synergistic immune activation, an increase in antigen presentation, and a reduction in tumor immune evasion. Improved overall and progression-free survival in various types of cancer is shown in clinical trials (e.g., CheckMate-067, IMbrave150, and PACIFIC). PD-L1 expression, TMB, and MSI are biomarkers that improve the selection of patients and forecast the response to treatment. Discussion: Although the approved combinations of nivolumab + ipilimumab and atezolizumab + bevacizumab have shown clinical success, toxicity, resistance, and high cost are also urgent issues. The combination of artificial intelligence and the use of biomarkers to personalize the treatment provides new ways of optimizing treatment. Conclusion: The future of precision oncology is combination immunotherapy, which offers sustained responses and survival advantages. Further studies on biomarkers, resistance, and costeffective approaches will influence their implementation into mainstream clinical practice.
Singh et al. (Tue,) studied this question.