Cancer remains the important cause for the mortality worldwide. In recent days, different biomedical strategies are in the limelight for the control of mortality due to cancer. As a promising strategy in cancer treatment, nano-formulations with advantages in drug delivery, health, and pharmacy are booming. The conventional nanocarrier continues, however, to suffer from low drug load efficiency, possible toxicity, unknown metabolism, and other uncertainties. To overcome these problems, carrier-free nanodrugs with desirable bioactivity were developed quickly and attracted considerable attention. In the meantime, the nanoarchitecture developed by a simple "natural" method with a multifunctional self-life has major advantages in multi-drug resistant synergistic cancer therapies and inhibition. Until now, the carrier-free nanoparticles for tumour therapy, phototherapy, chemotherapy, diagnostics, and synergistic therapy have made significant progress. In this review, the authors provide an integrated and detailed review of recent literature on nanodrug delivery systems composed of several active agents. © 2022 Elsevier B.V., All rights reserved.