We study analytically the evolution of superconductivity in clean quasi-two-dimensional multiband superconductors as the film thickness enters the nanoscale region by mean-field and semiclassical techniques. Tunneling into the substrate and finite lateral size effects, which are important in experiments, are also considered in our model. As a result, it is possible to investigate the interplay between quantum coherence effects, such as shape resonances and shell effects, with the potential to enhance superconductivity, and the multiband structure and the coupling to the substrate that tend to suppress it. The case of magnesium diboride, which is the conventional superconductor with the highest critical temperature, is discussed in detail. Once the effect of the substrate is considered, we still observe quantum size effects such as the oscillation of the critical temperature with the thickness but without a significant enhancement of superconductivity. In thin films with a sufficiently longer superconducting coherence length, it is, however, possible to increase the critical temperature above the bulk limit by tuning the film thickness or lateral size. arXiv:1311.0698v3 [cond-mat.mes-hall]