Biocompatible inorganic material-based nanosystems provide a novel choice to effectively circumvent the intrinsic drawbacks of traditional organic materials in biomedical applications, especially in overcoming the multidrug resistance (MDR) of cancer cells due to their unique structural and compositional characteristics, for example, high stability, large surface area, tunable compositions, abundant physicochemical multifunctionalities, and specific biological behaviors. In this review, we focus on the recent developments in the construction of inorganic nanoparticles-based drug codelivery nanosystems (mesoporous SiO2, Fe3O4, Au, Ag, quantum dots, carbon nanotubes, graphene oxide, LDH, etc.) to efficiently circumvent the MDR of cancer cells, including the well-known codelivery of small molecular anticancer drug/macromolecular therapeutic gene and codelivery of small molecular chemosensitizer/anticancer drug, and very recently explored codelivery of targeting ligands/anticancer drug, codelivery of energy/anticancer drug, and codelivery of contrast agent for diagnostic imaging and anticancer drug. The unsolved issues, future developments, and potential clinical translations of these codelivery nanosystems are also discussed. These elaborately designed biocompatible inorganic materials-based nanosystems offer an unprecedented opportunity and show the encouraging bright future for overcoming the MDR of tumors in clinic personalized medicine and the pharmaceutical industry.