A package structure with a heat spreader and manufacturing method thereof is disclosed. The package structure includes a substrate, a ground pad, a heat spreader, a non-conductive adhesive layer, and a pre-solder layer. A die is seated on the substrate, and the ground pad is disposed on the surface of the substrate. The manufacturing method of the package structure includes the following steps: (a) providing the substrate; (b) forming the pre-solder layer on the ground pad by solder paste printing; (c) forming the non-conductive adhesive layer on the substrate surface for being adjacent to the pre-solder layer by adhesive dispensing; (d) disposing the heat spreader onto the non-conductive layer and the pre-solder layer; and (e) heating the non-conductive adhesive layer for solidification and continuing to heat the pre-solder layer for solder reflow so that the heat spreader is adhered to the substrate via the non-conductive adhesive layer and coupled to the ground pad via the pre-solder layer.