Essentially, the "hot spot" is the intensive local electric field originating from the localized surface plasmon resonance (LSPR) of metal nanoparticles (NPs), and thus designing a special metal configuration to obtain the stronger electric-field enhancement naturally becomes a major reference in preparing SERS-active substrates. [1,2] Recently, many reports have demonstrated that the electric fields in the nanogaps between adjacent metal NPs can interact with each other, which are much stronger in contrast with that around the isolated NP. [4][5][6][7][8][9] Generally, metal nanoparticle clusters (NPCs) not only have abundant nano-interspaces which could provide various "hot spots," but also are equipped with bigger specific surface area, implying more probe molecules will be adsorbed on their surfaces, and thus are very popular in Raman enhancement. [1,7,10,11] Nowadays, except for the metal NPCs, semiconductor/metal heterostructures, such as Au/ZnO; Ag/TiO 2 ; etc., have also been regarded as one of the effective ways in tuning the LSPR due to the charge transfer (CT) effect between their interface. [12][13][14][15] Owing to the redistribution of electrons during the CT process, many analogous electric dipoles will form nearby the semiconductor/metal interface, which have been proved can contribute well to electric field enhancement, in other words are very useful in improving the EM as well. [12,16] In addition to the EM based substrates, bases with particular structures, e.g., the 3D SERS-active bases, have also become more and more highlighted recently. [13,[17][18][19][20] There are two major advantages for the 3D structure, one is the bigger specific surface area, and the other is the light-trapping effect. [18,21] Among them, the latter one can lead to the multiple reflections for incident lights in Raman base and finally improves the lights utilization. [20,22] One thing needs to be aware of is that besides the ultrasensitive detectability, a high-quality SERSactive substrate should also be equipped with many factors such as good stability, outstanding repeatability, well durability, economic-simple preparation process, and so on. [21,23] Therefore, designing a truly useful SERS-active substrate, a deceptively simple question, still faces enormous challenges today.Considering all the factors mentioned above, in this paper, a 3D Ag NPCs/CuO nanowires (NWs) heterostructure is designed A 3D pomegranate-like "Ag nanoparticle clusters/CuO nanowires" heterostructure is designed and prepared by a fast two-step method with assistance of capillarity in this paper. Owing to the abundant "hot spots" generated in the gaps of Ag nanoparticle clusters and the improved electromagnetic mechanism caused by the charge transfer effect between Ag/CuO interface, this heterostructure shows outstanding Raman performance with the enhancement factor as high as 3.30 × 10 9 . Both the formation process and the Raman enhancement mechanism of this heterostructure are meticulously analyzed, and the finite-different time-domain and f...