A cryogenic advanced propellant loading system is currently being developed at NASA. A wide range of applications and variety of loading regimes call for the development of computer assisted design and optimization methods that will reduce time and cost and improve the reliability of the APL performance. A key aspect of development of such methods is modeling and optimization of non-equilibrium two-phase cryogenic flow in the transfer line. Here we report on the development of such optimization methods using commercial SINDA/FLUINT software. The model is based on the solution of two-phase flow conservation equations in one dimension and a full set of correlations for flow patterns, losses, and heat transfer in the pipes, valves, and other system components. We validate this model using experimental data obtained from chilldown and loading of a cryogenic testbed at NASA Kennedy Space Center. We analyze sensitivity of this model with respect to the variation of the key control parameters including pressure in the tanks, openings of the control and dump valves, and insulation. We discuss the formulation of multi-objective optimization problem and provide an example of the solution of such problem.