Traditional liquid marbles (LMs), liquid droplets encapsulated by hydrophobic particles at the liquid-gas interface, are restricted by their short lifetime and low heat transfer efficiency. For the first time, we designed a new paradigm for LMs immersed in various liquid mediums with massive enhanced heat transfer and spatial recognition, while without compromising the structural integrity; the lifetime of the liquid marbles in liquid (LMIL) was extended by ~1000 times compared to classical LMs in air or naked droplets in organic reagents. The LMIL showed promising reverse structural re-configurability while under external stimuli and maintaining their functionality for a very long period of time (~ weeks). These superior behaviors were further exploited as a miniature reactor with prolonged lifetimes and excellent temperature control, combined with its feasible operation, will open up new opportunities in the advanced chemical and biomedical engineering fields. Here, we also showed that LMIL can be applied in methylene blue degradation and three dimensional (3D) in-vitro yeast cell cultures. Our findings have important implications for real-world use of liquid marbles, with a number of applications in cell culture technology, lab-in-a-drop, polymerization, encapsulation, formulation and drug delivery.