Constructing low‐dimensional heterojunctions via hybridizing 0D, 1D, and 2D building blocks is an effective means to devise higher‐order architectures with excellent photocatalytic reaction activities. Developing a versatile topology optimization strategy paves the way for guiding the rational structural design of a wide range of heterostructures. Herein, taking the ZnO‐CdS hybrids with mixed topology structures (including 0D‐1D, 0D‐0D, and 1D‐1D composites) as a model system, the work unveils a ubiquitous, yet unrecognized, topology dependence of photocatalytic performances and the 0D‐1D topology combination coupled with an annealing treatment gives rise to an optimal photocatalytic redox activity, far exceeding those of 0D‐0D and 1D‐1D counterparts. The 0D‐1D topology integrates the structural merits of both constituent units, where the 1D unit acts as a rigid matrix to allow the uniform dispersity of 0D units for exposing abundant active sites, and a mobile 0D unit contributes to the interfacial reconstruction for forming charge‐migration‐expediated heterointerfaces via thermal‐induced grain rotations. Such thermal‐annealing‐coupled topology optimization methodology shows applicability for a large spectrum of low‐dimensional heterojunctions, offering a prototype for the precise structural design of low‐dimensional heterojunctions with enhanced catalytic performance. [ABSTRACT FROM AUTHOR]