Heterogeneous nanoporous catalysts, such as zeolites, feature pores with diverse shapes and dimensions, providing distinct local chemistry and unique active site environments. Reactions within these confined spaces depend sensitively on the interactions between reactant molecules and the active-site environment, imparting enzyme-like selectivity but posing significant modeling challenges for large, flexible transition-state complexes. Addressing this necessitates a computational strategy that efficiently accounts for both electronic and confinement effects, which are critical in defining the interactions between reactant molecules and the active site environment. To understand and account for electronic effects, first-principles DFT calculations were employed to investigate competing aldol condensation and fission reactions, exploring various mechanistic pathways to elucidate competing routes. For condensation, the E1 mechanism on the tautomerized reactant exhibited the lowest intrinsic barrier, while Grob-like fragmentation presented the lowest barrier for fission. Transition-state selectivity was then investigated by examining the chemistries of the reactant molecules, revealing that electronic properties influenced the intrinsic barriers and overall selectivity, corroborated by experimental results. Probing into confinement effects, evidenced by reactions modeled inside zeolites, a computational method combining force field-based sampling and DFT-based transition state optimization was developed. This method generates low-energy configurations for transition-state complexes across the pore space of a nanoporous catalyst, which are then optimized using DFT calculations with the nudged elastic band method. This approach was applied to study catalytic cracking reactions, including mono- (protolytic) and bimolecular mechanisms inside MFI, FAU, LTA, and TON zeolites. For protolytic cracking of n-butane, smaller pores stabilized transition states enthalpically, while larger channels potentially offered better entropic stabilization. Site-dependent intrinsic barriers varied across different pore geometries, but ensemble-averaged values for each zeolite system were similar and aligned with experiments. For bimolecular cracking, comprising β-scission and hydride transfer, compact transition states were better stabilized in smaller pores, while larger transition states were favored in larger confinements. Site-dependent barriers displayed larger variations, with ensemble-averaged barriers depending on the morphology of the reactant and the zeolites. This study underscores the importance of considering both electronic and confinement effects in modeling catalytic reactions in nanoporous materials, offering insights into optimizing catalyst design for improved selectivity and efficiency.