Graphene oxide (GO) has attracted tremendous attention as a most promising nanomaterial among the carbon family since it emerged as a polynomial functional tool with rational applications in diverse fields such as biomedical engineering, electrocatalysis, biosensing, energy conversion, and storage devices. Despite having certain limitations due to its irreversible aggregation performance owing largely to the strong van der Waals interactions, efforts have been made to smartly engineer its surface chemistry for realistic multimodal applications. The use of such GO-based engineered devices has increased rapidly in the last few years, principally due to its excellent properties, such as huge surface area, honeycomb-like structure allowing vacant interstitial space to accommodate compounds, sp2 hybridized carbon, improved biocompatibility and cell surface penetration due to electronic interactions. Amongst multifaceted GO dynamics, in this review, attempts are made to discuss the advanced applications of GO or graphene-based materials (GBNs) in the biomedical field involving drug or therapeutic gene delivery, dual drug or drug-gene combination targeting, special delivery of drug cocktails to the brain, stimuli-responsive release of molecular payloads, and Janus-structured smart applications for polar-nonpolar combination drug loading followed by targeting together with smart bioimaging approaches. In addition, the advantages of duel-drug delivery systems are discussed in detail. We also discuss various electronic mechanisms, and detailed surface engineering to meet microcosmic criteria for its utilization, various novel implementations of engineered GO as mentioned above, together with discussions of its inevitable toxicity or disadvantages. We hope that the target audience, belonging to biomedical engineering, pharmaceutical or material science fields, may acquire relevant information from this review which may help them design future studies in this field.