We present the investigation of in vivo small model organisms, which are well established in biological and biomedical research, using a hybrid multiphoton and optoacoustic microscope (HyMPOM). The unique capabilities of HyMPOM for multimodal and potentially label-free signal acquisition, high resolution, as well as deep and fast imaging allow extraction of detailed information across large areas of living tissue on the microscale. Applying HyMPOM to living zebrafish-like fish larvae allowed exploration of the structural composition of the entire brain, including the brain vasculature and the neuronal network. Applying HyMPOM to the ears of living mice enabled accurate imaging of vasculature, connective tissue, keratinocytes, and sebaceous glands. The hybrid microscope proposed here constitutes a novel approach to explore small model organisms in vivo in great detail by revealing the spatial distribution and interplay of various tissue compartments on the microscale.