Bio-based natural resources are of significant scientific importance in this era due to their rich existence, renewability, easy accessibility, low cost, etc. Cellulose, the naturally occurring biopolymer abundant in plants and woods has been a potential starting material for valorization as their supply from the forest products industry and agricultural wastes is huge and inexpensive. Cellulose is a polymer substance, with the repeating units of monosaccharide containing secondary and tertiary–OH groups. These–OH groups are highly prone to undergo any modification using chemical reagents or by physical methods. Topochemical engineering is one strategy through which directed assembly of new guest molecules on substrate or disassembly of that host substrate units can be performed to produce multifunctional materials. This book chapter aims to disseminate the knowledge around topochemical engineering of cellulose-based functional materials with the emphasis on valorization techniques, material compositions, and applications, for the readers of sustainable biomaterials chemistry.