The development of interdisciplinary biomedical engineering brings significant breakthroughs to the field of cartilage regeneration. However, cartilage defects are considerably more complicated in clinical conditions, especially when injuries occur at specific sites (
e.g.
, osteochondral tissue, growth plate, and weight-bearing area) or under inflammatory microenvironments (
e.g.
, osteoarthritis and rheumatoid arthritis). Therapeutic implantations, including advanced scaffolds, developed growth factors, and various cells alone or in combination currently used to treat cartilage lesions, address cartilage regeneration under abnormal conditions. This review summarizes the strategies for cartilage regeneration at particular sites and pathological microenvironment regulation and discusses the challenges and opportunities for clinical transformation.