This paper presents a methodology for the optimal design and operation of man-portable power generation devices based on fuel cells. To illustrate the methodology, we focus on a simple process that consists of a fuel processing reactor, a solid-oxide fuel cell (SOFC) and two burners in a stack. Hydrogen is produced from ammonia decomposition, while butane is catalytically oxidized to produce heat and maintain the stack at a sufficiently high temperature. First, a model is formulated for predicting the steady-state performance of the process, which relies on intermediate fidelity modeling assumptions. Subsequently, this model is used as a basis to study and determine the optimal design and operation of the overall system. The optimization problem is formulated so that the specific energy density of the fuels (ammonia and butane) is maximized, while meeting a specified power demand, maintaining the stack at its thermal equilibrium, and satisfying tight constraints in regard to the emission of both ammonia and nitric oxide gases. The effects of the operating temperature and nominal power demand on the performance of the system are analyzed thoroughly, with emphasis placed on several counter-intuitive results that provide insight into the design. Finally, a parametric study is presented, which considers the effect of uncertainties in the heat loss coefficients and the exchange current densities, as well as that of the electrolyte thickness, on the optimal design and operation of the process.