Musculoskeletal diseases are increasing the prevalence of physical disability worldwide. Within the body, musculoskeletal soft and hard tissues integrate through specific multitissue transitions, allowing for body movements. Owing to their unique compositional and structural gradients, injuries challenge the native interfaces and tissue regeneration is unlikely to occur. Tissue engineering strategies are emerging to emulate the physiological environment of soft-to-hard tissue interfaces. Advances in biomaterial design enable control over biophysical parameters, but biomaterials alone are not sufficient to provide adequate support and guide transplanted cells. Therefore, biological, biophysical, and biochemical tools can be integrated into a multifactorial toolbox, steering prospective advances toward engineering clinically relevant soft-to-hard tissue interfaces.