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The application of nanoparticles as nanomedicines, particularly for targeted and efficacious delivery of drugs is an expanding platform in the field of cannabinoid and pharmaceutical drug delivery. By refocusing the route of drug administration beyond the oral gut pathway, this technology provides significant advancements that is especially relevant for cancer treatments. Orally administered drugs face significant challenges as they traverse the gastrointestinal tract (GIT) and are subject to first pass GIT metabolism. Physiological conditions encountered in the GIT such as food effects, hormones, gastric pH, emptying time, and intestinal transit time vary widely across individuals. Fluid composition and enzymatic activity in the small intestine and large bowel also influence drug dissolution and absorption. These factors in conjunction with the intestinal cohort of bacteria can metabolize drugs before absorption, contributing to poor and variable drug bioavailability, which can be exacerbated by gut dysbiosis. Drug delivery that bypasses the oral-GIT route and hence first pass metabolism offers a plausible solution for enhanced safety and drug efficacy.