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The van Est map is a map from Lie groupoid cohomology (with respect to a sheaf taking values in a representation) to Lie algebroid cohomology. We generalize the van Est map to allow for more general sheaves, namely to sheaves of sections taking values in a (smooth or holomorphic)   $G$  -module, where   $G$  -modules are structures, which differentiate to representations. Many geometric structures involving Lie groupoids and stacks are classified by the cohomology of sheaves taking values in   $G$  -modules and not in representations, including   $S^1$  -groupoid extensions and equivariant gerbes. Examples of such sheaves are   $\mathcal{O}^*$   and   $\mathcal{O}^*(*D)\,,$   where the latter is the sheaf of invertible meromorphic functions with poles along a divisor   $D\,.$   We show that there is an infinitesimal description of   $G$  -modules and a corresponding Lie algebroid cohomology. We then define a generalized van Est map relating these Lie groupoid and Lie algebroid cohomologies and study its kernel and image. Applications include the integration of several infinitesimal geometric structures, including Lie algebroid extensions, Lie algebroid actions on gerbes, and certain Lie   $\infty $  -algebroids.

Cohomology of Lie Groupoid Modules and the Generalized van Est Map