A complete fingerprint of a tissue sample requires a detailed description of its cellular and extracellular components while minimizing artifacts. We introduce the application of a novel scanning electron microscope (airSEM™) in conjunction with light microscopy for functional analysis of tissue preparations at nanometric resolution (<10 nm) and under ambient conditions. Our metal-staining protocols enable easy and detailed visualization of tissues and their extracellular scaffolds. A multimodality imaging setup, featuring airSEM™ and a light microscope on the same platform, provides a convenient and easy-to-use system for obtaining structural and functional correlative data. The airSEM™ imaging station complements other existing imaging solutions and shows great potential for studies of complex biological systems.