HIV remains a global health challenge, affecting millions of individuals worldwide. While combination antiretroviral therapy (cART) significantly reduces viral loads to undetectable levels, it does not eradicate the virus completely, and a compromised host immune system persists. Traditionally, HIV-1 research has largely focused on elucidating the mechanisms of viral replication, characterising host immune responses, specifically inflammation, and developing effective antiretroviral therapies. However, comparatively less emphasis has historically been placed on understanding the metabolic alterations associated with HIV-1 infection. Metabolomics, a powerful tool that provides a functional understanding of the systemic metabolic changes induced by HIV and cART, is increasingly recognised for its potential to reveal the complex interplay between chronic inflammation, metabolic reprogramming, and long-term health outcomes. This chapter explores the critical metabolic pathways disrupted by HIV infection in the modern cART era, focusing on amino acid, glucose, microbiome, and lipid metabolism. Using metabolomic profiling, this chapter highlights persistent immunometabolic dysfunctions in people living with HIV, highlighting pathways of comorbidity risk and offering insights into therapeutic interventions to improve patient outcomes in the modern cART era.