Cancer immunotherapy has transformed the oncology landscape by harnessing the immune system’s ability to recognize and eliminate malignant cells. This paradigm shift from conventional therapies to biologically targeted interventions underscores a new era in cancer therapy. From its early theoretical and experimental foundations to the groundbreaking clinical applications we see today, immunotherapy has revolutionized cancer treatment. Landmark achievements, particularly immune checkpoint inhibitors targeting the PD-1/PD-L1 axis or CTLA-4, have demonstrated durable responses across various cancers, validating the therapeutic potential of immune modulation. Building on these advances, multiple approaches such as CAR-T cells, have provided unprecedented efficacy in hematologic malignancies. At the same time, cancer vaccines and oncolytic viruses bring innovative approaches to tackling solid tumors. Despite challenges, including immune-related toxicities and resistance mechanisms, ongoing advancements in biomarkers, combination therapies, and novel immune modulators address these limitations, paving the way for more personalized and resilient treatment responses. This chapter highlights the evolution of cancer immunotherapy and its transition to engineered cell-based therapies for cancer, tracing its journey from conceptual origins to scientific milestones.