Abstract: Chimeric antigen receptor T-cell therapy has improved outcomes in several B-cell malignancies, but responses in solid tumors remain inconsistent and often short-lived. Antigen heterogeneity, tumor-intrinsic resistance, inadequate infiltration, immunosuppression, metabolic competition, T-cell exhaustion, and toxicity limit efficacy; addressing all these issues simultaneously through a single engineering approach is challenging. In recent years, progress has been made in target screening, multi-antigen recognition, receptor signaling optimization, improvements in cell subsets and manufacturing processes, local delivery, armoring and metabolic engineering, and combination therapy. Some products have entered the randomized controlled trial and clinical application phases, though their benefits remain limited by patient selection, manufacturing lead times, prior treatments, and toxicity. This article reviews the biological rationale, representative clinical evidence, and translational challenges for optimizing the efficacy of chimeric antigen receptor T-cell therapy in solid tumors, focusing on patient stratification, target selection, product design, administration and combination therapy, efficacy monitoring, and safety management, to provide guidance for future research and clinical evaluation.