High-Pressure Partial Oxidation (HP-POX) of natural gas is one of the techniques in the synthesis gas production by non-catalytic reforming. On the path to emissions reduction, all operating facilities must be optimized to satisfy environmental regulations. In a rapidly changing economic and political environment, technological development from lab-scale to demo-scale, and industrial-scale is no longer feasible. Therefore, new research and design methods must be applied. One of such methods commonly used in science and industry is numerical modeling, which utilizes Computational Fluid Dynamics (CFD), Reduce Order Models (ROMs), kinetic, and equilibrium models. The CFD models provide details about flow field, temperature distribution, and species conversion. However, the computational effort required to conduct such calculations is significant. The computationally expensive CFD models cannot be effectively used in the reactor optimization. Herewith, other modeling techniques utilizing kinetic and equilibrium models do not provide necessary details for process optimization and can only be used for adjustments of boundary conditions, investigation of specific processes occurring in the reactor, or development of sub-models for CFD. A numerical investigation was conducted to validate existing CFD models against benchmark experiments. The results reveled that the CFD model is sensitive to modeling parameters, when simulating complex flows where turbulence-chemistry interaction occurs. Moreover, it was shown that the results sensitivity increases along with the oxidizer/fuel inlet velocities ratio. Based on the conducted experiments, the CFD model validation resulted in definition of the modeling parameters suitable for modeling of HP-POX of natural gas. Based on the validated CFD model, a ROM for HP-POX of natural gas was developed. The model assumes that the reactor consists of several zones characterized by specific conversion processes. Moreover, the model considers inlet streams dissipation upon the injection, and includes several optimization stages that allows model adjustments for any reactor geometry and boundary conditions. It was shown that the developed ROM can reproduce global reactor characteristics at non-equilibrium conditions unlike other ROMs, kinetic, or equilibrium models. Moreover, the validation against CFD results showed that the ROM can correctly account for the \gls{rtd} in the reactors of different geometries and volumes without extensive additional optimization. Finally, new experiments were designed and conduced at semi-industrial HP-POX facility at TU Bergakademie Freiberg. The experiments aimed to study the influence of different oxidizer/fuel velocities ratios on the reactants mixing and process characteristics at high operating pressures. The high velocity difference between oxidizer and fuel was achieved by injection of High-Velocity Oxidizer (HVO). The experiments showed no significant influence of the HVO on the global reactor characteristics and overall species conversion process. However, the numerical analysis of the experimental results demonstrated that the oxidation zone is affected by the oxidizer inlet velocity, and becomes less efficient in the fuel conversion when the oxidizer/fuel inlet velocities ratio is increased. In summary, a sophisticated numerical model validation was conducted and sensitivity of the numerical results to the modeling parameters was carefully studied. The novel natural gas conversion technique was experimentally studied. Based on the conducted experiments and numerical evaluation a ROM was developed. The ROM is capable of producing high accuracy results and greatly decreases the computational effort and time needed for reactor development and optimization.