BACKGROUND: Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by bone marrow infiltration, monoclonal immunoglobulin production, and multisystem damage. Proteasome inhibitors (PIs) such as bortezomib, carfilzomib, and ixazomib have significantly improved progression-free and overall survival in MM patients. However, drug resistance and adverse effects-including peripheral neuropathy and cardiotoxicity-remain major limitations to long-term disease control. OBJECTIVE: This review aims to comprehensively evaluate the synergistic mechanisms and therapeutic potential of Traditional Chinese Medicine (TCM) in combination with PIs for the treatment of MM, from molecular insights to translational outcomes. METHODS AND SCOPE: We synthesized findings from preclinical studies, pharmacological investigations, and cohort analyses that examine the interplay between TCM bioactives and PI-based regimens. Focus is given to the modulation of MM-related signaling pathways (eg, NF-κB, STAT3, PI3K/Akt), apoptotic cascades, proteasomal degradation processes, and the bone marrow microenvironment. RESULTS: Evidence suggests that specific TCM compounds-such as curcumin, baicalein, icariin, and berberine-can potentiate PI-induced cytotoxicity, reverse resistance mechanisms, reduce inflammatory damage, and protect against PI-associated toxicities. Several Chinese herbal formulations, including Fuzheng Peiyuan and Huanglian Jiedu decoctions, have demonstrated immunomodulatory and anti-myeloma effects in vivo and in human cohorts. These synergistic actions may enhance the efficacy and tolerability of PIs in MM therapy. CONCLUSION: Integrating TCM with proteasome inhibitors represents a promising strategy to optimize MM treatment by simultaneously targeting malignant cells and the tumor microenvironment. Further mechanistic research and well-designed clinical trials are warranted to validate and standardize this combinational approach for broader clinical adoption.