We present an updated determination of nuclear parton distributions (nPDFs) from a global NLO QCD analysis of hard processes in fixed-target lepton-nucleus and proton-nucleus together with collider protonnucleus experiments. In addition to neutral-and charged-current deep-inelastic and Drell-Yan measurements on nuclear targets, we consider the information provided by the production of electroweak gauge bosons, isolated photons, jet pairs, and charmed mesons in proton-lead collisions at the LHC across centre-ofmass energies of 5.02 TeV (Run I) and 8.16 TeV (Run II). For the first time in a global nPDF analysis, the constraints from these various processes are accounted for both in the nuclear PDFs and in the freeproton PDF baseline. The extensive dataset underlying the nNNPDF3.0 determination, combined with its model-independent parametrisation, reveals strong evidence for nuclear-induced modifications of the partonic structure of heavy nuclei, specifically for the small-x shadowing of gluons and sea quarks, as well as the large-x anti-shadowing of gluons. As a representative phenomenological application, we provide predictions for ultra-high-energy neutrino-nucleon cross-sections, relevant for data interpretation at neutrino observatories. Our results provide key input for ongoing and future experimental programs, from that of heavy-ion collisions in controlled collider environments to the study of high-energy astrophysical processes.