In recent years, an encouraging breakthrough in the synthesis of immobilized enzymes in flower‐shaped called “organic‐inorganic hybrid nanoflowers (hNFs)” with greatly enhanced catalytic activity and stability were reported. Although, these hNFs were discovered by accident, the enzymes exhibited highly enhanced catalytic activities and stabilities in the hNFs compared with the free and conventionally immobilized enzymes. Herein, we rationally utilized the catalytic activity of the hNFs for analytical applications. In this comprehensive review, we covered the design and use of the hNFs as novel versatile sensors for electrochemical, colorimetric/optical and immunosensors‐based detection strategies in analytical perspective.