The current industrial revolution signifies the high-value of biocatalysis engineering. Over the past decade, multiple micro- and nanostructured materials have been attempted for immobilization of enzymes to improve their catalytic properties. Conventional immobilization strategies result in improved stability, while insolubilized enzymes generally lost their activity compared to free counterparts. Recently, a new generation organic-inorganic hybrid nanoflowers with unique properties have received great attention as a novel and incentive immobilization approach owing to their simple fabrication, high biocatalytic efficiency, and enzyme stabilizing capability. The hybrid nanoflowers biocatalytic system implicates metal ions and biomolecules (enzymes). In contrast to free or conventionally immobilized enzymes, single enzyme or multi enzyme-incorporated flowers-like hybrid nanoconstructs demonstrated elevated catalytic activities and stabilities over a very broader range of experimental conditions, i.e., pHs, temperatures and salt concentration. This review discusses the recent developments in the fabrication strategies to diversifying nanoflowers, types, characteristics, and applications of organic-inorganic hybrid nanoflowers as a host platform to engineer different kinds of enzymes with requisite functionalities for biocatalysis applications in different sectors of the modern world. Based on experimental and theoretical literature data, the review is wrapped up with concluding remarks and an outlook in terms of upcoming challenges and prospects for their scale-up applications.