Porous nanostructures exhibit remarkable nanoplatforms for payload delivery to diseased cells with high loading capacity, favorable release profiles, improved hemocompatibility, biocompatibility, and safe clearance after biodegradation. Metal–organic frameworks (MOFs), periodic mesoporous organosilica (PMO), or biodegradable periodic mesoporous organosilica (BPMO) epitomize a similar category of structured and crystalline porous coordinated compounds or nanocomposites. Additionally, their elevated surface-to-volume ratio, customizable porous configurations, and convenient attachment of favorable ligands to the central metal ions enhance drug loading and release, further demonstrating their potential for drug delivery applications. This review focuses on these materials, including Fe-MOFs, Cu-MOFs, Zr-MOFs, PMO and BPMO, along with multicompartmental mesoporous nanostructures, detailing their specific engineering, chemistry, and optimal drug delivery applications.