This combined experimental and computational study is aimed at elucidating the structure and reactivity of heterogeneous molecular clusters. We report results for the system para-chlorofluorobenzene/methanol (pClFB/MeOH). Particularly, three different van der Waals (vdW) isomers of the neutral (1:1) aggregate (pi,sigma(F),sigma(Cl)) have been assigned by comparison of experimental infrared frequencies in the O-H and C-H stretch regions measured by IR/R2PI depletion spectroscopy with calculated frequencies at MP2/6-31+G(d) and B3LYP/6-31+G(d) level. The isomers are weakly hydrogen-bonded complexes with methanol's OH group coordinated toward the aromatic pi-electron cloud, the fluorine or the chlorine substituent, respectively. This assignment is corroborated by the UV and IR spectra of the corresponding monosubstituted benzene/methanol complexes. After resonant photoionization of pClFB .(MeOH)(n), for n=1 besides vdW fragmentation, no chemical reactivity was observed for any isomer. The investigation of aggregates with n greater than or equal to 5 indicated a substitution reaction taking place to produce chloroanisole(+), emphasizing the importance of neutral precursor cluster size over cluster structure for intracluster ion-molecule reactions.