The tumor microenvironment (TME) is increasingly understood as a metabolically dynamic ecosystem in which local metabolite availability, composition, and trafficking shape immune cell fitness and therapeutic responsiveness. Against the backdrop of the global obesity epidemic, obesity-associated systemic metabolic dysregulation has been implicated in tumor initiation and progression and may also influence the immune contexture and treatment responsiveness of tumors. This Review examines how obesity-derived systemic metabolites may modulate anti-tumor immunity and influence cancer immunotherapy, with particular emphasis on pathways involved in metabolic reprogramming and TME remodeling. We further discuss intervention strategies spanning (i) upstream metabolite generation, (ii) systemic-to-local trafficking into the TME, and (iii) direct functional antagonism within the TME.