Abstract:Fluorescence Molecular Tomography (FMT) is a promising technique for non-invasive 3D visualization of fluorescent probes, but its reconstruction remains challenging due to the inherent ill-posedness and reliance on inaccurate or often-unknown tissue optical properties. While deep learning methods have shown promise, their supervised nature limits generalization beyond training data. To address these problems, we propose $\mu$NeuFMT, a self-supervised FMT reconstruction framework that integrates implicit neural-based scene representation with explicit physical modeling of photon propagation. Its key innovation lies in jointly optimize both the fluorescence distribution and the optical properties ($\mu$) during reconstruction, eliminating the need for precise prior knowledge of tissue optics or pre-conditioned training data. We demonstrate that $\mu$NeuFMT robustly recovers accurate fluorophore distributions and optical coefficients even with severely erroneous initial values (0.5$\times$ to 2$\times$ of ground truth). Extensive numerical, phantom, and in vivo validations show that $\mu$NeuFMT outperforms conventional and supervised deep learning approaches across diverse heterogeneous scenarios. Our work establishes a new paradigm for robust and accurate FMT reconstruction, paving the way for more reliable molecular imaging in complex clinically related scenarios, such as fluorescence guided surgery.