An ongoing grand challenge in bottom-up synthetic biology is designing and constructing synthetic cells with life-like properties. Despite the significant advances, even the most highly integrated synthetic cell does not come close to living entities. One of the main differences is that biological cells are dynamic and show self-regulating behavior, while synthetic cellular mimics will eventually reach a static state and exhibit unidirectional responses to perturbation. To this end, the next milestone for bottom-up synthetic biology will be the development of sustainable synthetic cellular systems that can show functional dynamic behavior. Here, we review the engineering strategies to design and construct such functional synthetic cellular systems and the challenges and potential future opportunities in this field are discussed.