Cr

The design of magnetic materials is often enabled by rigid crystal frameworks that permit site-selective chemical control without compromising structural integrity, as exemplified by Heusler alloys. Extending this framework-driven design paradigm to low-dimensional systems remains challenging due to the limited structural complexity of many van der Waals (vdW) magnets. Here, using first-principles density functional theory, we establish rhombohedral Cr₂X₃ (X = S, Se, Te) as a connectivity-encoded inorganic platform for designing non–van der Waals magnetic materials. Focusing on site-selectively substituted Cr₃TMSe₆ (TM = V, Mn, W), we show that the mixed face-sharing and edge-sharing Cr–Se octahedral framework remains thermodynamically accessible and dynamically, thermally, and kinetically robust upon substitution. While the Cr–Se network continues to dominate the electronic structure, transition-metal substitution acts as a controlled perturbation that systematically reshapes magnetic ground states, exchange networks, and magnetic anisotropy through distinct orbital and spin–orbit coupling mechanisms. These results demonstrate how framework topology and site chemistry cooperatively govern magnetism in non–van der Waals layered systems, establishing Cr₂Se₃ as a generalizable platform for materials-by-design beyond conventional 2D magnets.