In this work, a computational approach is proposed in order to help establish the effect of various flow-drilling screw process and material parameters on the quality and the mechanical performance of the resulting flow-drilling screw joints. Toward that end, a sequence of three distinct computational analyses is developed. These analyses include the following: (a) finite element modeling and simulations of the flow-drilling screw process; (b) determination of the mechanical properties of the resulting flow-drilling screw joints through the use of three-dimensional, continuum finite element–based numerical simulations of various mechanical tests performed on the flow-drilling screw joints and (c) determination, parameterization and validation of the constitutive relations for the simplified flow-drilling screw connectors, using the results obtained in (b) and the available experimental results. The availability of such connectors is mandatory in large-scale computational analyses of whole-vehicle crash or even in simulations of vehicle component manufacturing, for example, car-body electro-coat paint-baking process. In such simulations, explicit three-dimensional representation of all flow-drilling screw joints is associated with a prohibitive computational cost. The approach developed in this work can be used, within an engineering-optimization procedure, to adjust the flow-drilling screw process and material parameters (design variables) in order to obtain a desired combination of the flow-drilling screw joint mechanical properties (objective function).