Metabolically heterogeneous tumors could rely on “metabolic symbiosis” to mutually regulate the access to extracellular nutrients between glycolytic and oxygenated tumor cells for impeding the development of therapies which aim at metabolic vulnerabilities. Herein, a yeast@MOF bioreactor has been designed as a tumor metabolic symbiosis disruptor to deprive the energy supply of both glycolytic and oxygenated tumor cells for the potent inhibition of metabolically heterogeneous tumors. The yeast@MOF bioreactor integrated the biocompatible probiotic yeast with functional enzyme-encapsulated metal-organic-framework. The bioreactors could competitively consume glucose to reduce their diffusion to glycolytic tumor cells and cut down the tumorous lactate pool. Meanwhile, they could decompose lactate to prevent their exploitation by oxygenated tumor cells. Moreover, the bioreactor could elevate oxidative stress for further amplifying the tumor inhibition effect. We anticipate that this study will not only promote the design of living biomaterials-based therapy, but also facilitate the development of metabolic interventions-based cancer therapy.