We study the effect of donor-acceptor orientation on solvent-dependent three-photon transition probabilities (δ(3PA)) of representative through-space charge-transfer (TSCT) systems, namely, doubly positively charged [2,2]-paracyclophane derivatives. Our cubic response calculations reveal that the value of δ(3PA) may be as high as 10(6) a.u., which can further be increased by a specific orientation of the donor-acceptor moieties. To explain the origin of the solvent cum orientation dependency of δ(3PA), we have calculated different three-photon tensor components using a two-state model, noting that only a few tensor elements contribute significantly to the overall δ(3PA) value. We show that this dependence is due to the large dipole moment difference between the ground and excited states of the systems. The dominance of a few tensor elements indicates a synergistic involvement of π-conjugation and TSCT in the large δ(3PA) of these systems.