We report a synthesis route to two-dimensional PbSe, HgSe, ZnSe, SnSe, and Cu-Zn-Sn-Se (CZTSe) nanomaterials based on cation exchange (CE) reactions. This approach includes two steps: it starts with the synthesis of hexagonal, up to several micrometers large yet approx. 5 nm-thick CuSe nanosheets (NSs), followed by CE of the host copper ions with the desired guest cation (Pb2+, Hg2+, Zn2+, or Sn4+). In the case of CZTSe, both guest cations can be added simultaneously since the variation of the guest cation ratio and reaction time can lead to various compositions. Mild reaction conditions allow for a preservation of the size and the 2D shape of the parent NSs accompanied by corresponding changes in their crystal structure. We furthermore demonstrate that the crystal structure of CuSe NSs can be rearranged even without addition of guest cations in the presence of tri-n-octylphosphine. Thus, the obtained NSs were further subjected to ligand exchange reactions in order to replace insulating bulky organic molecules on their surface with compact iodide and sulfide ions, a step crucial for the application of nanomaterials in (opto)electronic devices. The resulting NS dispersions were processed into thin films by spray-coating onto commercially available interdigitated platinum electrodes. Light response measurements of PbSe and CZTSe NS-films demonstrated their potential for applications as light-sensitive materials in photodetection or photovoltaics.