The efficient and reproducible crystallisation of a polymorph showing the desired properties and functionalities is crucial in a variety of fields, such as the pharmaceutical sector. Characterising thermodynamics and mechanisms of polymorphic transitions at the molecular level is thus a key step towards developing a rational design of crystallisation processes and products. Despite its relevance, a systematic computational analysis of polymorphism and polymorphic transitions still represents a major challenge. In this thesis, metadynamics is employed in combination with state-of-the-art techniques, such as committor analysis and Markov State Models, to provide insight into polymorphism in molecular systems. The first part of the work focuses on packing polymorphism. The investigation of the transition between phases I and III in bulk carbon dioxide aims at testing a set of computational tools able to characterise in detail thermodynamics and mechanism of polymorphic transitions. This set-up is then applied and further developed for the study of CO2 confined in cylindrical nanopores, unveiling a complex landscape of ordered structures, unaccessible in unconfined conditions. Next, the serendipitous and irreproducible discovery of a new polymorph of succinic acid, γ, provides a challenging context to tackle the study of conformational polymorphism. Form γ presents folded conformers in its unit cell, while the other known polymorphs show planar molecules. From molecular dynamics and metadynamics, γ appears labile and metastable, a characteristic that might hinder its crystallisation. The study of the conformational behaviour of succinic acid in water reveals fast interconversions within a network of nine conformers, both folded and planar, among which the folded conformation observed in γ is the most thermodynamically stable. The high flexibility of this molecule is relevant in determining the nucleation mechanism. Simulations of supersaturated solutions and of crystal seeds dissolution suggest that nucleation cannot be classical, but it is rather likely to be a multi-step process.