This article introduces a single-cell metabolic imaging platform that enables high-resolution and high-specificity imaging of lipid metabolism in human-derived model systems. The platform uses an azide-tagged infrared (IR) probe to selectively detect newly synthesized lipids in cells and tissues, while fluorescence imaging allows for cell-type identification. The method was tested in various human-relevant models, including neuroglioma cells, human induced pluripotent stem cells (hiPSCs), hiPSC-derived microglia, and brain organoids. The study demonstrated that newly synthesized lipids can be directly visualized in these models, revealing differences in lipid metabolism between cell types and under different conditions. For example, progranulin-knockdown hiPSCs and their derived microglia showed increased lipid metabolism, while neurons in brain organoids exhibited lower lipid metabolism compared to astrocytes. The platform also showed that lipid metabolism in GRN-deficient cells was significantly altered, with increased newly synthesized lipids and lipid accumulation. The study highlights the potential of this platform for cell-type-specific metabolic imaging and its application in understanding metabolic heterogeneity in human diseases. The method uses optical photothermal infrared (OPTIR) microscopy combined with IR probes, offering sub-micrometer resolution and compatibility with fluorescence imaging. The platform's ability to detect lipid metabolism at the single-cell level provides new insights into metabolic processes and has potential applications in studying a wide range of metabolic-related diseases.This article introduces a single-cell metabolic imaging platform that enables high-resolution and high-specificity imaging of lipid metabolism in human-derived model systems. The platform uses an azide-tagged infrared (IR) probe to selectively detect newly synthesized lipids in cells and tissues, while fluorescence imaging allows for cell-type identification. The method was tested in various human-relevant models, including neuroglioma cells, human induced pluripotent stem cells (hiPSCs), hiPSC-derived microglia, and brain organoids. The study demonstrated that newly synthesized lipids can be directly visualized in these models, revealing differences in lipid metabolism between cell types and under different conditions. For example, progranulin-knockdown hiPSCs and their derived microglia showed increased lipid metabolism, while neurons in brain organoids exhibited lower lipid metabolism compared to astrocytes. The platform also showed that lipid metabolism in GRN-deficient cells was significantly altered, with increased newly synthesized lipids and lipid accumulation. The study highlights the potential of this platform for cell-type-specific metabolic imaging and its application in understanding metabolic heterogeneity in human diseases. The method uses optical photothermal infrared (OPTIR) microscopy combined with IR probes, offering sub-micrometer resolution and compatibility with fluorescence imaging. The platform's ability to detect lipid metabolism at the single-cell level provides new insights into metabolic processes and has potential applications in studying a wide range of metabolic-related diseases.