In this paper, a unique hybrid approach to design and synthesize 2D/3D Al2O3-ZnO nanostructures by simultaneous deposition is presented. Pulsed laser deposition (PLD) and RF magnetron sputtering (RFMS) methods are redeveloped into a single tandem system to create a mixed-species plasma to grow ZnO nanostructures for gas sensing applications. In this set-up, the parameters of PLD have been optimized and explored with RFMS parameters to design 2D/3D Al2O3-ZnO nanostructures, including nanoneedles/nanospikes, nanowalls, and nanorods, among others. The RF power of magnetron system with Al2O3 target is explored from 10 to 50 W, while the ZnO-loaded PLD’s laser fluence and background gases are optimized to simultaneously grow ZnO and Al2O3-ZnO nanostructures. The nanostructures are either grown via 2-step template approach, or by direct growth on Si (111) and MgO substrates. In this approach, a thin ZnO template/film was initially grown on the substrate by PLD at ~300 °C under ~10 milliTorr (1.3 Pa) O2 background pressure, followed by growth of either ZnO or Al2O3-ZnO, using PLD and RFMS simultaneously under 0.1–0.5 Torr (13–67 Pa), and Ar or Ar/O2 background in the substrate temperate range of 550–700 °C. Growth mechanisms are then proposed to explain the formation of Al2O3-ZnO nanostructures. The optimized parameters from PLD-RFMS are then used to grow nanostructures on Au-patterned Al2O3-based gas sensor to test its response to CO gas from 200 to 400 °C, and a good response is observed at ~350 °C. The grown ZnO and Al2O3-ZnO nanostructures are quite exceptional and remarkable and have potential applications in optoelectronics, such in bio/gas sensors.