Nanoscale medicine confers passive and active targeting potential. The development of nanomedicine is however met with processing, handling and administration hurdles. Excessive solid nanoparticle aggregation and caking result in low product yield, poor particle flowability and inefficient drug administration. These are overcome by converting the nanoparticles into a microscale dosage form via agglomeration or compaction techniques. Agglomeration and compaction nonetheless predispose the nanoparticles to risks of losing their nanogeometry, surface composition or chemistry being altered and negating biological performance. This study reviews risk factors faced during agglomeration and compaction that could result in these changes to nanoparticles. The potential risk factors pertain to materials choice in nanoparticle and microscale dosage form development, and their interplay effects with process temperature, physical forces and environmental stresses. To render the physicochemical and biological behaviour of the nanoparticles unaffected by agglomeration or compaction, modes to modulate the interplay effects of material and formulation with processing and environment variables are discussed.