We argue that the large suppression of the ψ(2S) inclusive cross-section relative to the J/ψ inclusive cross-section in proton-nucleus (p+A) collisions can be attributed to factorization breaking effects in the formation of quarkonium. These factorization breaking effects arise from soft color exchanges between charm-anticharm pairs undergoing hadronization and comoving partons that are long-lived on time scales of quarkonium formation. We compute the short distance pair production of heavy quarks in the Color Glass Condensate (CGC) effective field theory and employ an improved Color Evaporation Model (ICEM) to describe their hadronization into quarkonium at large distances. The combined CGC+ICEM model provides a quantitative description of J/ψ and ψ(2S) data in proton-proton (p+p) collisions from both RHIC and the LHC. Factorization breaking effects in hadronization, due to additional parton comovers in the nucleus, are introduced heuristically by imposing a cutoff Λ, representing the average momentum kick from soft color exchanges, in the ICEM. Such soft exchanges have no perceptible effect on J/ψ suppression in p+A collisions. In contrast, the interplay of the physics of these soft exchanges at large distances, with the physics of semi-hard rescattering at short distances, causes a significant additional suppression of ψ(2S) yields relative to that of the J/ψ. A good fit of all RHIC and LHC J/ψ and ψ(2S) data, for transverse momenta P ⊥ ≤ 5 GeV in p+p and p+A collisions, is obtained for Λ ∼ 10 MeV. A c c ∼ t t ∼ t c t f · · · FIG. 1: (Color online) Schematic diagram of Onium production in p+A collisions. The red blob represents parton hard scattering at short distances. Vertical gluons represent multiple gluon scattering (with typical net momentum exchange of order Qs, the saturation scale) off the target nucleus, expressed through a lightlike Wilson line. Soft gluon exchange between produced cc pair and comover spectators at larger distances are shown as orange vertical gluons. The three time scales (tt, tc, t f ) discussed in the text are also illustrated in the figure.Recently, the PHENIX Collaboration at RHIC reported on measurements of ψ(2S) production in d+Au collisions with center-of-mass energy √ s N N = 0.2 TeV/nucleon [28]. They found that in rare events corresponding to a large number of collisions, the ψ(2S) yield is significantly suppressed relative to p+p collisions. This suppression is greater than that seen for the J/ψ yield. The observation of ψ(2S) suppression was corroborated by the ALICE Collaboration in p+Pb collisions at √ s N N = 5.02 TeV/nucleon [29]. They found that the suppression parameter for ψ(2S), R ψ(2S) pA