The search for the smallest quark-gluon plasma (QGP) droplets in nature has motivated recent small collisions system programs at RHIC and LHC. Unambiguous identification of jet quenching due to final-state interactions is key to confirming QGP formation in these reactions. We compute the nuclear modification factors $R_{AA}$ and $R_{p(d)A}$ of charged hadrons and heavy flavor mesons in large (Au-Au, Xe-Xe, Pb-Pb) and small ($d$-Au, $p$-Pb, O-O) colliding systems, respectively. Our results include the Cronin effect and initial-state parton energy loss in cold nuclear matter. In the final state, hard partons undergo collisional energy loss and branching that was recently derived using Soft-Collinear-Effective-Theory with Glauber Gluon (SCET$_{\rm G}$). In large colliding systems, medium-modified QCD evolution of the fragmentation functions dominates the nuclear correction. As the system size decreases, we find that cold nuclear matter effects, collisional energy loss, and QGP-induced radiations can become equally important. A systematic scan over the medium size and mass/flavor dependence of $R_{AA}$ provides the opportunity to separate these individual contributions and identify QGP signatures in small systems. Predictions for $R_{AA}^{h}$, $R_{AA}^{D}$, $R_{AA}^{B}$ in O-O collisions at $\sqrt{s}=7$ TeV are presented with and without the formation of a QGP and contrasted with the corresponding $R_{p(d)A}$ calculations. Upcoming single-hadron measurements at the LHC will not only test the O-O predictions for both light and heavy flavor production, but will shed light on the possibly very different dynamics of $p$-A and A-A reactions at similar soft particle production multiplicities.