Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of cancer treatment that can significantly impact patients' quality of life. This study investigated the effects of targeting metabolic pathways on bortezomib-induced neuropathic pain and tumor growth using a Lewis lung carcinoma (LLC) mouse model, while also exploring potential sex differences in tumor burden and the efficacy of metabolic interventions. Our findings demonstrate that metformin and aerobic glycolysis inhibitors, such as dichloroacetate (DCA) and oxamate, effectively attenuate bortezomib-induced neuropathic pain without compromising the anticancer efficacy of bortezomib in both male and female tumor-bearing mice. Interestingly, the LLC mouse model exhibited a paraneoplastic neuropathy-like phenotype, suggesting its potential as a tool for studying this condition. Significant sex differences were observed in tumor growth, with male mice exhibiting larger tumors compared to females. Furthermore, sex-specific responses to metabolic interventions were noted, with oxamate being more effective in alleviating allodynia in males and metformin and DCA showing greater efficacy in reducing tumor growth in females. These findings highlight the importance of considering sex as a biological variable in preclinical and clinical studies investigating cancer biology, CIPN, and potential therapeutic interventions.