Abstract Photoacoustic microscopy (PAM), a fruitful application modality for photoacoustic imaging, is capable of directly measuring optical absorption properties in skin tissue, providing high-contrast, high-resolution medical images as well as functional and pathologic information. However, optical attenuation and unknown optical and acoustic nonuniformities limit its imaging performance in deep tissue regions. New instrumentation, image reconstruction, and artificial intelligence methods are being investigated to overcome these limitations, and a reliable PAM simulation tool is required for the effective implementation of these methods. In this paper, we propose and validate a 3D quantitative computational multispectral PAM imaging model. It provides a theoretical basis for the application of quantitative PAM in skin diagnosis and aids in the development and optimization of PAM devices, as well as the acquisition of deep learning datasets.