As life expectancy continues to increase, so do disorders related to the musculoskeletal system. Orthopedics-related impairments remain a challenge, with nearly 325 thousand and 120 thousand deaths recorded in 2019. Musculoskeletal system, including bone and cartilage tissue, is a living system in which cells constantly interact with the immune system, which plays a key role in the tissue repair process. An alternative to bridge the gap between these two systems is exploiting nanomaterials, as they have proven to serve as delivery agents of an array of molecules, including immunomodulatory agents (anti-inflammatory drugs, cytokines), as well as having the ability to mimic tissue by their nanoscopic structure and promote tissue repair per se. Therefore, this review outlooks nanomaterials and immunomodulatory factors widely employed in the area of bone and cartilage tissue engineering. Emerging developments in nanomaterials for delivery of immunomodulatory agents for bone and cartilage tissue engineering applications have also been discussed. It can be concluded that latest progress in nanotechnology have enabled to design intricate systems with the ability to deliver biologically active agents, promoting tissue repair and regeneration; thus, nanomaterials studied herein have shown great potential to serve as immunomodulatory agents in the area of tissue engineering.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.