Trends in Nanotechnology to improve therapeutic efficacy across special structures

•This manuscript describes various biological barriers in targeting tumor microenvironment.•Discusses the various geometry and size of nanoparticle on the targeted therapies and their role in cargo delivery.•Explores potential opportunities in tumor microenvironment to overcome various natural hindrances.•Describes various trending and promising mechanistic approaches to deal with these obstacles and landscape the therapeutic road with nanotechnology.•Finally, presents future directions for nanotechnology and tumor microenvironment to explore new ways.