Cell therapies including stem cell therapies and engineered cell therapies are widely accepted nowadays, especially the autologous CAR T cell therapies with multiple FDA approval in the past decade. However, the ex vivo engineered cell therapies, including autologous and allogenic CAR T cell therapies face multiple challenges in manufacturing, logistics and patient accessibilities. With the emerging novel technologies on in vivo delivery systems, now in vivo cell engineering is no longer a science fiction, and is happening in real life. This provides an alternative solution for patients who are not able to receive proper treatment due to the hurdles of ex vivo cell therapies. The field is rapidly evolving and a few in vivo CAR T cell therapies are already in the clinic. Although the clinical efficacy is yet to be determined, it is shining light from the end of the tunnel for patients, who are desperately waiting for curative therapies.