Certain microalgae species have gained traction in the biofuel and food/feed sectors due to their ability to accumulate large amounts of intracellular lipids. However, the extraction of lipids from microalgae is hindered by the presence of complex and recalcitrant cell walls that act as a barrier to mass transfer. This paper examines the intricate details of microalgae cell walls of species belonging to three genera—Nannochloropsis, Scenedesmus, and Schizochytrium—known for their high total lipid contents and omega-3 polyunsaturated fatty acid contents, thus having dual potential for both biofuel and food/feed application. An overview of the techniques used to analyse the cell walls, followed by a detailed description of the cell wall architecture of the three genera and the growth conditions that affect the ultrastructure and composition of their cell walls, is presented. Since cell wall disruption is a crucial step in recovering intracellular products from microalgae biomass, different cell-disruption technologies are also reviewed, focusing specifically on approaches that can be applied directly to wet biomass without the need for biomass drying, thus exerting a low-energy footprint. Enzymatic treatment is operated under mild conditions and offers a promising wet route for targeted recovery of intracellular products from microalgae with minimal side reactions and risk of product degradation. The high cost of enzymes can be mitigated by reducing enzyme requirements through the adoption of a minimal design approach that uses the cell wall composition as the basis to direct enzyme choice and dosage. Different enzyme-recycling and immobilisation strategies to reduce enzyme requirements and improve commercial scalability are also reviewed. Finally, the paper provides a summary of the current state-of-the-art in direct biological approaches using algicidal bacteria and fungi to achieve cell disruption. Overall, the paper provides a roadmap for a more efficient cell disruption of microalgae.