Osteochondral tissue engineering (OC-TE) seeks to rebuild the coupled cartilage–bone unit within an immune milieu that can determine integration or failure. Immunomodulation is treated as a primary design variable. Immune fundamentals are outlined with emphasis on macrophage polarization dynamics, stage-specific roles of neutrophils and T cells, and the paracrine immunoregulation provided by mesenchymal stem/stromal cells (MSCs). Biomaterial strategies that purposefully steer immunity are reviewed, including composition and surface chemistry, approaches to minimize foreign body reaction, incorporation of immunoactive ions or nanoparticles, and the use of decellularized matrices that bias toward constructive remodeling. Targeted cytokine delivery is presented as a complementary lever: interleukin-4 and interleukin-10 to promote pro-resolving macrophage states, interleukin-1 receptor antagonist to blunt catabolic signaling, and carefully dosed transforming growth factor-β1 to support matrix synthesis. Controlled-release designs, microspheres, stimuli-responsive linkers, and sequential depots are considered with attention to timing and dose. Architectural innovations include multilayer constructs that assign anti-inflammatory function to the cartilage side and osteogenic support to the bone side, graded porosity to organize infiltration and angiogenesis, mechanically tuned stress-relaxing hydrogels to temper inflammatory tone, and temporal “smart” scaffolds that adapt output to local cues. Cell-based and acellular biologics extend this repertoire, covering MSCs, engineered cells, extracellular vesicles, and immune-inspired decoys. Evidence from preclinical models, ex vivo human tissues, and early clinical injections illustrates feasibility, while current use of autologous biologics and decellularized grafts provides translational footholds. Persisting challenges include patient heterogeneity, scheduling of dose and duration, infection risk, manufacturing control, and regulatory complexity. Emerging directions span gene-activated scaffolds, mechano-immunomodulatory materials, immune-mimetic nanotechnologies, and data-guided design. The chapter consolidates a toolbox for constructing osteochondral implants that cooperate with host immunity to achieve durable regeneration.