Abstract: Emerging single cell technologies that capture three-dimensional genomic interactions (scHi-C) alongside DNA methylation present new opportunities for integrative analysis. We introduce Muscle, a semi-nonnegative joint decomposition method that leverages the inherent tensor structure of scHi-C to unify these modalities, revealing key cell type–specific signals and inter-modality associations. To further address high-dimensional tensor regression challenges arising in the 3D genome context, we propose Sparse Higher Order Partial Least Squares (SHOPS) for variable selection, dimension reduction, and response denoising. Together, these methods underscore the promise of tensor-based approaches for elucidating the interplay between the epigenome and three-dimensional genome organization at the single cell level.