Recent developments in 2D magnetic materials have motivated the search for new van der Waals magnetic materials, especially Ising-type magnets with strong magnetic anisotropy. Fe-based MPX ( = transition metal, = chalcogen) compounds such as FePS and FePSe both exhibit an Ising-type magnetic order, but FePSe receives much less attention compared to FePS. This work focuses on establishing the strategy to engineer magnetic anisotropy and exchange interactions in this less-explored compound. Through chalcogen and metal substitutions, the magnetic anisotropy is found to be immune against S substitution for Se whereas tunable only with heavy Mn substitution for Fe. In particular, Mn substitution leads to a continuous rotation of magnetic moments from the out-of-plane direction toward the in-plane. Furthermore, the magnetic ordering temperature displays non-monotonic doping dependence for both chalcogen and metal substitutions but due to different mechanisms. These findings provide deeper insight into the Ising-type magnetism in this important van der Waals material, shedding light on the study of other Ising-type magnetic systems as well as discovering novel 2D magnets for potential applications in spintronics.