An important and unavoidable aspect of the game is providing security to the colony by constructing defense walls and towers. You must remember that the towers can't shoot over rocks and forest. You should always construct quadruple stone walls and if you can afford it, even many-segmented defenses (the first line of defense can be for example Great Ballista and the second - Executor). Take advantage of the Shocking Tower - set them on the first line of defense due to their small range. The electricity can kill many weaker zombies and it repels stronger ones. Prepare yourself for placing the Shocking Tower as they consume plenty of energy (30). You should also switch the priority of all towers (double left click on a tower marks all of them) so that they attack the most dangerous zombie. This option still makes them shoot the weaker zombies for as long as there are no stronger ones. If you also have defensive units, set their priority as well.
While spreading the colony and forming the defense, notice the choke points, strategic points and passages. You can build a strong defense there at low cost. Take advantage of the fact that the zombies are always trying to reach the Command Center through the shortest path. Each new zombie wave gives you information about the probable path the zombies will take to your colony, enabling you to create better defenses on that path. Don't use Stake Traps, they aren't worth the price unless you lack iron to place their better version and the final wave is bound to start soon. You should always try to upgrade ballistas and place Executors. If you lack resources, ballistas will be effective as well. They are cheap and their upkeep is low.
When the last waves start, it's a good time to switch your army into the stationary mode. If possible, build towers for your snipers in order to increase their range. Keep the archers in the back and send them where there are problems with defenses. You can also use Titans as a backup. They are small, walking executors that are quite fast. It is a very good idea to add Thanatos to your snipers near the walls. 2-4 of these units per a piece of the wall would be enough.
Micromanagement of units is very important during the final wave. If you see that a horde of zombies is soon going to end on one side of the colony and the towers are managing on their own, then move your units to a different place where the defenses are struggling.
If the zombies somehow manage to break your defenses, you can still use walls that you haven't removed while increasing the size of your colony. You can pause the game and quickly add walls and towers and remove some of the buildings in order to stop the disease from spreading.