Optical waveguides are essential components in integrated photonic circuits and communication devices. Despite recent advances in both inorganic and organic materials, the use of Coordination Polymers (CPs) as single-crystal optical waveguides remains in its infancy but shows great potential. This study aims to gain insight into several design factors for the preparation of single crystal CPs to be used as active optical waveguides. These factors include the nature of the ligand-based emission (investigated both experimentally and theoretically), chemical functionalization at the metal center with ancillary building blocks, and molecular arrangements within the crystal lattice. The CPs presented in this study demonstrate exceptional light propagation performances, with optical losses ranking among the lowest ever reported for CPs and single-crystal organic waveguides. The systematic comparison of the performance of the supramolecular assemblies presented here allowed us to draw significant conclusions, providing valuable insights for the future design of single crystal CPs and optimization of their optical waveguiding performance.