Methods, apparatus, systems and articles of manufacture to optimize execution of a machine learning model are disclosed. An example apparatus includes a quantizer to quantize a layer of a model based on an execution constraint, the layer of the model represented by a matrix. A packer is to pack the quantized layer of the matrix to create a packed layer represented by a packed matrix, the packed matrix having non-zero values of the matrix grouped together along at least one of a row or a column of the matrix. A blocker is to block the packed layer into a blocked layer by dividing the non-zero values in the packed matrix into blocks. A fuser is to fuse the blocked layer into a pipeline. A packager is to package the pipeline into a binary.