Organic-inorganic multiferroics are promising for the next generation of electronic devices. To date, dozens of organic-inorganic multiferroics have been reported; however, most of them show a magnetic Curie temperature much lower than room temperature, which drastically hampers their application. Here, by performing first-principles calculations and building effective model Hamiltonians, we reveal a molecular orbital-mediated magnetic coupling mechanism in two-dimensional Cr(pyz)2 (pyz = pyrazine) and the role that the valence state of the molecule plays in determining the magnetic coupling type between metal ions. Based on these, we demonstrate that a two-dimensional organic-inorganic room-temperature multiferroic, Cr(h-fpyz)2 (h-fpyz = half-fluoropyrazine), can be rationally designed by introducing ferroelectricity in Cr(pyz)2 while keeping the valence state of the molecule unchanged. Our work not only reveals the origin of magnetic coupling in 2D organic-inorganic systems but also provides a way to design room-temperature multiferroic materials rationally.