AbstractMelt electrospinning writing (MEW) that processes molten polymers has emerged as a reliable method to fabricate high‐fidelity fibrous tissue scaffolds for investigation of cell biological performance as a function of structural features. However, most of the current investigations have focused on the scaffolds with homogeneous features, which can yield homogeneous cell performance outcomes as expected. In contrast, spatially heterogeneous scaffolds with well‐defined, non‐uniform pore attributes can serve as biomimetic, multiplexed platforms for biological investigations. In this study, an analytically derived general heterogeneous toolpath design model is introduced. In addition to the traditional orthogonal fiber orientations, fiber placement along diagonal directions is introduced to generate semi‐0‐θ patterned or 0‐θ patterned heterogeneous scaffolds. By specifying model parameters and hence tuning the relative location of the diagonal fibers to orthogonal fibers, the customized heterogeneous scaffolds produced can possess at most three different pore morphologies. The various distributions of different pore morphologies within one scaffold are subsequently mapped by an advanced mathematical matrix method for the first time. Moreover, the proportion of different pore morphologies of semi‐0‐θ patterned scaffolds can be obtained numerically. Finally, this proposed analytical design model is preliminarily validated by fabrication using a MEW printing process.