Birefringence and second harmonic generation are important to realizing the phase-matching capability and laser frequency conversion efficiency in a nonlinear optical (NLO) crystal. Heteroleptic tetrahedra have usually been used to design and explore birefringent or NLO materials, such as fluorooxo-heteroleptic tetrahedra BO x F 4−x (x = 1, 2, 3), PO x F 4−x (x = 2, 3), SO 3 F and other groups SiO 4−x N x (x = 1, 2, 3), PO 4−x S x (x = 1, 2, 3). Generally, heteroleptic tetrahedra exhibit larger microscopic properties than those of normal oxy-tetrahedra MO 4 (M = B, P, S, Si, etc.), which will improve the birefringence or NLO coefficients in a crystal. In this review, we systematically investigated the microscopic properties of heteroleptic tetrahedra which cover the deep-ultraviolet to the mid-infrared region, including SiO 4−x Nx (x = 2, 3), and BO 3 N. The structure-performance relationships of the related compounds with the above-mentioned heteroleptic tetrahedra were discussed through first-principles calculations. According to the computational results, some compounds with heteroleptic tetrahedra have good optical performances and can be used as potential ultraviolet or mid-infrared optical functional materials. This work will provide helpful insights into rational design and synthesis of new optical functional materials containing heteroleptic tetrahedra.