Nanotechnology aims to utilize chemical functional groups-conjugated nanoparticles for measuring physical and chemical quantities at the intracellular level. This demands a basic understanding of luminescent nanoparticles’ interfacial energy transfer process. Therefore, a new technique is introduced to engineer complex photon upconverting nanostructures and alter their photonic properties. In this study, an intraparticle-energy transfer process (i-ETP) is presented by a complex nanoarchitecture consisting of core-multiple shells, spatially separated Er3+, Yb3+, Tm3+, and Nd3+ ions in a multi-layered NaYF4 host structure. The main concept is that by placing certain lanthanide ions (Ln3+) in specific spatial positions of the unique nanostructures, the luminescence profiles can be changed, and energy transfer can be blocked or reversed based on need. Additionally, the study offers a qualitative analysis of how to regulate energy transfer at the nanoscale by engineering the core’s structure along with double and triple shell layers by Ln3+ for their specific functions. The findings enhance understanding of Ln3+ ion behavior in intraparticle light management upon 980 nm light excitation. The intra-cellular compatibility of the nanoparticles is verified through cytotoxicity and cellular uptake investigation using multicolor 3D live-cell imaging.