We study the possibility of realizing an effective sequestering between visible and hidden sectors in generic heterotic string models, generalizing previous work on orbifold constructions to smooth Calabi-Yau compactifications. In these theories, genuine sequestering is spoiled by interactions mixing chiral multiplets of the two sectors in the effective Kahler potential. These effective interactions however have a specific current-current-like structure and can be interpreted from an M-theory viewpoint as coming from the exchange of heavy vector multiplets. One may then attempt to inhibit the emergence of generic soft scalar masses in the visible sector by postulating a suitable global symmetry in the dynamics of the hidden sector. This mechanism is however not straightforward to implement, because the structure of the effective contact terms and the possible global symmetries is a priori model dependent. To assess whether there is any robust and generic option, we study the full dependence of the Kahler potential on the moduli and the matter fields. This is well known for orbifold models, where it always leads to a symmetric scalar manifold, but much less understood for Calabi-Yau models, where it generically leads to a non-symmetric scalar manifold. We then examine the possibility of an effective sequestering by global symmetries, and argue that whereas for orbifold models this can be put at work rather naturally, for Calabi-Yau models it can only be implemented in rather peculiar circumstances.