This work provides an insight into how the molecular interactions influence macroscale properties of two materials: swelling clay and oil shale. Swelling clays cause enormous damage to infrastructure: buildings, roads, and bridges. Understanding the mechanisms are essential to prevent the detrimental effects and use of these clays for engineering applications. Our group studied the effect of fluid polarity on sodium montmorillonite (Na-MMT) swelling clay mineral using molecular modeling and experiments for bridging the molecular level behavior with the microstructure, swelling pressure, permeability, and compressibility. Various polar fluids (Dielectric Constant 110 to 20) found in landfill leachates are used. Our molecular dynamics (MD) simulations show that the nonbonded interactions of Na-MMT with polar fluids are higher than with low and medium polar fluids. These results are consistent with the results from Fourier transform infrared (FTIR) spectroscopy experiments. The polarity of the fluids and the fluid content influence the interlayer spacing, interlayer modulus, nonbonded interactions, and conformation as well as the shear strength parameters, the angle of internal friction (φ) and cohesion (c). Furthermore, the unconfined compressive strength experiments are used to evaluate the undrained cohesion at various swelling level. The nanomechanical properties, the modulus of elasticity (E) and hardness (H), of the undisturbed dry and saturated Na-MMT at various level of swelling are evaluated using nanoindentation experiments for the first time. The undrained cohesion, modulus of elasticity, and hardness decrease with increase in swelling level. Swelling controls the microstructure of Na-MMT clay, and the clay particles breakdown into smaller sizes with increase in swelling level. The Green River Formation located in the United States is the richest oil shale deposit in the world. Oil shale contains clay minerals, bitumen, and kerogen—a precursor to crude oil. A three-dimensional (3D) kerogen model is built from seven fragments, and the interactions of kerogen with Na-MMT is investigated using MD simulations to understand how the kerogen is bound to the clay mineral. The nonbonded interactions between Na-MMT and kerogen as well as among kerogen fragments are found. This work seeks to develop new methods to extract kerogen economically and efficiently.