CAR-T cell therapy has shown strong curative potential and is a critical component in treating B-cell malignancies. Effective CAR-T cell manufacturing is essential for product safety, efficacy, and patient access. This review discusses major process parameters and next-generation strategies in autologous CAR-T cell manufacturing. Key factors include the choice of starting cell population, T-cell activation methods, CAR transgene delivery, and ex vivo cell expansion. The starting cell population, such as CD4+ and CD8+ T cells, significantly impacts product quality. T-cell activation is crucial for CAR transgene integration and expansion, often using magnetic beads or polymeric nanomatrices. Viral vectors like lentivirus and retrovirus are commonly used for CAR transgene delivery, but non-viral methods like CRISPR/Cas9 and transposons are being explored for safer and more precise integration. Ex vivo expansion is optimized with cytokines and supplements to increase T-cell numbers. Product release testing ensures safety, purity, potency, identity, and stability. Next-generation strategies aim to accelerate manufacturing, reduce costs, and improve patient access. Automated manufacturing and in vivo cell production are promising approaches to overcome current limitations. Overall, advancements in CAR-T cell manufacturing are vital for expanding therapeutic applications and improving patient outcomes.CAR-T cell therapy has shown strong curative potential and is a critical component in treating B-cell malignancies. Effective CAR-T cell manufacturing is essential for product safety, efficacy, and patient access. This review discusses major process parameters and next-generation strategies in autologous CAR-T cell manufacturing. Key factors include the choice of starting cell population, T-cell activation methods, CAR transgene delivery, and ex vivo cell expansion. The starting cell population, such as CD4+ and CD8+ T cells, significantly impacts product quality. T-cell activation is crucial for CAR transgene integration and expansion, often using magnetic beads or polymeric nanomatrices. Viral vectors like lentivirus and retrovirus are commonly used for CAR transgene delivery, but non-viral methods like CRISPR/Cas9 and transposons are being explored for safer and more precise integration. Ex vivo expansion is optimized with cytokines and supplements to increase T-cell numbers. Product release testing ensures safety, purity, potency, identity, and stability. Next-generation strategies aim to accelerate manufacturing, reduce costs, and improve patient access. Automated manufacturing and in vivo cell production are promising approaches to overcome current limitations. Overall, advancements in CAR-T cell manufacturing are vital for expanding therapeutic applications and improving patient outcomes.