This work provides the design methodology of the radioisotope thermophotovoltaic system (RTPV) using spectral control for space missions. We focus on the feasibility of a practical system by using two-dimensional micro-patterned photonic crystal emitters, selecting the proper TPV cell and insulation material to exclude material incompatibilities, to optimize the system efficiency by impedance matching, and to design the radiator with minimum mass. In the last section, we present a design example based on the tested InGaAsSb cells. We show computationally that using the experimentally tested InGaAsSb cells, the RTPV generator is expected to reach an efficiency of 8.6% and a specific power of 10.1 W/kg with advanced radiators. Using the more efficient InGaAs cells, the system can expect to triple the figure of merits of the Radioisotope Thermoelectric Generator (RTG), promising to reach ~18% and 21 W/kg, respectively. With a high performance device, the results of this work can lead to a functional prototype for further research focusing on manufacturability and reliability.