Microelectronic assemblies are basically compounds of several high precision materials with quite different Young's moduli and thermal expansion coefficients (CTE). Additionally, various kinds of inhomogeneity, residual stresses generated by several steps of the manufacturing process and extreme thermal environmental conditions contribute to interface delamination, chip cracking and fatigue of solder interconnects.For that reason, numerical investigations by means of nonlinear FEA together with conventional strength hypotheses are frequently used for design optimizations and sensitivity analyses. So, design studies on the basis of parameterized FE-models and DOE/RSM-approaches help to optimize electronic components at early phases of the product development process. But, this methodology typically bases on classical stress/strain strength evaluations or/and life time estimations of solder interconnects using modified Coffin-Manson approaches, whereas delamination or bulk fracture mechanisms usually remain unconsidered.By means of a representative microelectronics assembly this contribution is going to figure out and discuss ways and challenges of using numerical fatigue evaluation and fracture mechanics approaches in connection with parameterized finite element modeling based DOE/RSM-concepts. That is, the evaluation of mixed mode interface delamination phenomena utilizing the VCCT-methodology, classical strength hypotheses along with fracture mechanics approaches and modified Coffin-Manson thermal fatigue estimation of solder joints will be simultaneously applied within a multi-objective optimization towards a thermo-mechanical reliable design.