This review paper analyzes the development of advanced class polylactide (PLA) materials through a combination of stereocomplexation and nanocomposites approaches. The similarities in these approaches provide the opportunity to generate an advanced stereocomplex PLA nanocomposite (stereo-nano PLA) material with various beneficial properties. As a potential “green” polymer with tunable characteristics (e.g., modifiable molecular structure and organic–inorganic miscibility), stereo-nano PLA could be used for various advanced applications. The molecular structure modification of PLA homopolymers and nanoparticles in stereo-nano PLA materials enables us to encounter stereocomplexation and nanocomposites constraints. The hydrogen bonding of D- and L-lactide fragments aids in the formation of stereococomplex crystallites, while the hetero-nucleation capabilities of nanofillers result in a synergism that improves the physical, thermal, and mechanical properties of materials, including stereocomplex memory (melt stability) and nanoparticle dispersion. The special properties of selected nanoparticles also allow the production of stereo-nano PLA materials with distinctive characteristics, such as electrical conductivity, anti-inflammatory, and anti-bacterial properties. The D- and L-lactide chains in PLA copolymers provide self-assembly capabilities to form stable nanocarrier micelles for encapsulating nanoparticles. This development of advanced stereo-nano PLA with biodegradability, biocompatibility, and tunability properties shows potential for use in wider and advanced applications as a high-performance material, in engineering field, electronic, medical device, biomedical, diagnosis, and therapeutic applications.