A systematic design approach has been outlined for the design of manifold-coupled multiplexers taking into consideration a brief review of different types of multiplexer configurations. The precise approach in optimizing parts of the multiplexer separately in repeated cycles has proved to be very effective for most practical applications, while converging upon an optimal solution. This technique can be applied to manifold mulitplexers that incorporates an arbitrary number of channels, regardless of their bandwidths and channel separations. The use of space-mapping optimization techniques is applied in EM simulation, manifold junctions, and channel filters where EM-based simulators are used to fine-model each multiplexer channel and coupling matrix representation is used in coarse-model the performance. The effects of dispersion and spurious modes are taken into consideration in this design procedure as a result of which the overall design and final tuning time can be reduced significantly.