Abstract: Multiple myeloma (MM) is a common hematological malignancy. MM exhibits remarkable spatiotemporal heterogeneity across its clinical presentations and molecular features. Drug resistance and relapse remain persistent clinical challenges, rendering MM still incurable. Temporally, the disease progresses dynamically from an asymptomatic stage without treatment indication to symptomatic active disease, and from post-remission states to relapsed refractory phases—a process intrinsically accompanied by complex clonal evolution and immunoediting. Spatially, it presents a highly heterogeneous distribution pattern, manifesting as varying degrees of organ damage, circulating tumor plasma cells, extramedullary lesions, and disturbances in the immune microenvironment. Grounded in Professor Zhou Zhongying’s “cancerous toxin” theory and Academician Tong Xiaolin’s “state target differentiation and treatment” framework, and incorporating the spatiotemporal perspective alongside the theories of five zang-organs, qi-blood-body fluids, and yin-yang balance, this paper constructs a “cancerous toxin-state target-spatiotemporal” three-dimensional pathogenesis model. The model identifies “healthy qi deficiency with cancerous toxin” as the core pathogenesis, with phlegm, blood stasis, and heat as interwoven pathogenic elements. It further proposes the following dynamic evolutionary characteristics for MM: healthy qi deficiency with pathogen aggregation giving rise to cancerous toxin; intermingling of phlegm, stasis, and toxin with latent heat accumulation; cancerous toxin lurking and prevention of relapse after remission; exuberant heat eroding the bones with exhaustive deficiency involving all five zang-organs. At the theoretical level, this framework macroscopically captures the dynamic evolution of the composite pathogenesis characterized by “healthy qi deficiency, toxin accumulation, and pathogen aggregation”, while microscopically elucidating the mechanisms underlying “systemic deficiency with local tumorous heat”. At the clinical level, it identifies the nature and spatiotemporal localization of the cancerous toxin, systematically expounds the application of the core prescription—Xuanbi Xiaoliu Fang—and integrates clinical features with molecular and imaging assessments. This enables full-cycle, stage-specific treatment tailored to individual spatiotemporal profiles, with screening of key targeted agents to achieve disease-target synergy and explore a scientific pathway for precision intervention. At the mechanistic level, the scientific connotations of this model are elucidated from the perspectives of proteostasis, immune remodeling, the tumor microenvironment, metabolic reprogramming, and epigenetics. Through the close integration of theory, clinical practice, and translational mechanisms, this paper aims to provide a systematic theoretical framework and practical strategies for integrated Chinese-Western medicine management of MM.