Poly(methyl methacrylate) (PMMA) is widely used in orthopedic applications, including bone cement in total joint replacement surgery, bone fillers, and bone substitutes due to its affordability, biocompatibility, and processability. However, the bone regeneration efficiency of PMMA is limited because of its lack of bioactivity, poor osseointegration, and non-degradability. The use of bone cement also has disadvantages such as methyl methacrylate (MMA) release and high exothermic temperature during the polymerization of PMMA, which can cause thermal necrosis. To address these problems, various strategies have been adopted, such as surface modification techniques and the incorporation of various bioactive agents and biopolymers into PMMA. In this review, the physicochemical properties and synthesis methods of PMMA are discussed, with a special focus on the utilization of various PMMA composites in bone tissue engineering. Additionally, the challenges involved in incorporating PMMA into regenerative medicine are discussed with suitable research findings with the intention of providing insightful advice to support its successful clinical applications.