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Despite the remarkable clinical success of immune checkpoint inhibitors, significant challenges such as primary resistance, limited T-cell infiltration in solid tumors, and severe immune-related adverse events persist. As the second volume of \u201cThe Role of Immunotherapy in Cancer Therapy and Its Challenges\u201d Community Series, this review systematically evaluates the recent breakthroughs and persistent hurdles in CAR-T cell therapy and bispecific antibodies (BsAbs). We emphasize a critical strategic shift: transitioning these potent modalities from late-stage salvage therapies to earlier treatment lines to preserve the patient\u2019s immune repertoire and improve long-term survival. Furthermore, we dissect the molecular engineering of innovative CAR-T and BsAb constructs\u2014such as armored CARs and multi-specific engagers\u2014specifically designed to antagonize the immunosuppressive tumor microenvironment (TME) in solid cancers. A central focus is placed on the optimization of combination strategies, including the synergistic integration of cellular therapies with hematopoietic stem cell transplantation (HSCT) and targeted agents to eradicate minimal residual disease (MRD). By synthesizing the latest clinical data on overall survival (OS) and progression-free survival (PFS), we propose an evidence-based framework for sequential therapy and toxicity management. 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