Many cross-layer design approaches for wireless multimedia transmission over various networks have been proposed. Truly cross-layer design solutions require joint optimization of multimedia coding, transport/network layer, medium access layer, and physical layer transmission strategies and protocols. The solution often becomes impractical because: (i) its computational complexity is high; and (ii) it needs to be recomputed as some inputs, such as the content characteristics or network conditions change. To this effect, we propose a novel framework for cross-layer design, which features: (i) the joint design strategy selection being adaptive not only to network conditions but also to multimedia content characteristics; (ii) the joint design strategy selection being based on off-line learning to address the computational complexity issue; and (iii) the off-line learning stage employing a new multiple objective optimization solution.