This paper discusses a reliability based optimisation modelling approach demonstrated for the design of a SiP structure integrated by stacking dies one upon the other. In this investigation the focus is on the strategy for handling the uncertainties in the package design inputs and their implementation into the design optimisation modelling framework. The analysis of fhermo-mechanical behaviour of the package is utilised to predict the fatigue life-time of the lead-free board level solder interconnects and warpage of the package under thermal cycling. The SiP characterisation is obtained through the exploitation of Reduced Order Models (ROM) constructed using high fidelity analysis and Design of Experiments (DoE) methods. The design task is to identify the optimal SiP design specification by varying several package input parameters so that a specified target reliability of the solder joints is achieved and in the same time design requirements and package performance criteria are met.