Nutriomic analysis is a postgenomic-based study of nutritious components (nutriome). There is a need for an in vitro digestion and absorption model to unravel interactive factors varying nutriome release from various food materials that cannot be directly studied in humans. Effects of processing and in vitro digestion steps on carotenoid, sugar, and organic acid release from tomato, papaya, and mango products were comprehensively studied for the first time in this research. In vivo chewing experiments using 24 healthy adult volunteers was carried out prior to chewing simulation. Microscopy showed that cutting and blending alone were unlikely to mimic chewing at swallowing point. Using general linear model (GLM) ANOVA and principal component analysis (PCA), effects of interaction between digestion steps and processing types on the nutriome release were significant (p < 0.05) when 90% particles of 0.5 (dried) and 1.5 cm (fresh) were digested in vitro. Generally, dried and fresh fruits released lower levels of nutriome components than juices. PCA indicated nutriome release from tomato products was affected by the factors studied more than those from papaya and mango products. Fruit type is the main determinant factor relative to processing and digestion steps because it determines the extent of matrix that breaks down and consequent nutriome diffusion rates. It is predicted that pectin plays a role in determining the rate of nutriome release and absorption, which requires further investigation.