Zero-dimensional (0D)-2D nanostructures, which combine the efficient light-harvesting properties of 0D nanocrystals (NCs) and the ultrafast carrier transfer of 2D materials, have been widely used in optoelectronic devices. Although the most common way to fabricate 0D-2D nanostructures consists of a mixing process, the limited loading efficiency of NCs and the poor 0D-2D interface hinder the efficient photo-carrier generation and fast carrier separation/transfer in such systems. Herein, the in situ synthesis of CsPbBr3/BP heterostructures via a hot-injection method was presented, revealing that both the formation process of CsPbBr3 NCs and the CsPbBr3/black phosphorous (BP) interfaces presented pronounced changes. This led to a larger CsPbBr3 NC size, higher CsPbBr3 NC loading efficiency, optimized combination of CsPbBr3 and BP at the interface, and enhanced carrier transfer properties. In addition, the in situ synthesized CsPbBr3/BP heterostructure was used as a photoactive material for the fabrication of photodetectors, which showed high detectivity (D*) of 2.6 × 1011 Jones. This work highlights a novel strategy to optimize the 0D-2D heterostructure interface and to promote its carrier transfer efficiency, broadening the field of the applications of mixed-dimensional nanostructures.