Beat the boss from the inside
Once you defeat the previous boss in the shooting stage, your craft will touch down on the surface of the head, and you will have to enter inside the giant organism to take it down once and for all. Inside, you will find a collection of biological agents working to support the life of the very creature you are now attacking, and they won't be so keen to just let you come in and start destroying things. The final stage itself contains no branches or multiple pathways. Although steps divide one section from another, it is a relatively straight shot from beginning to end. You will have to contend with many things like tricky jumps and attacking membranes, but the number one most difficult threat in the game are the antibodies.
Antibodies alternate between appearing from the left and the right. When one is defeated, the next one comes in from the other side. The only thing that will delay the appearance of the next antibody is if it drops an item; as long as the dropped item is still on the screen, the next one will not appear. Antibodies float over to your character and try to stick to them as long as possible. They continuously drain health from your character. They cannot be hit when they are so close up. You can only really hit them when they are still a small distance away from you. Goemon's tobacco pipe is useful against them, as is King Kong's punch and Moai's head-butt. However, if one or more antibodies get stuck on you, the best way to deal with them is to use Simon and his boomerang. Fire off one boomerang, and jump up just as it's about to come back to you. The boomerang will hit the antibody who is just starting to rise to catch up to you. It will take two boomerang hits to knock them down, but it's your best chance for survival.
Don't waste too much effort
It's true that there are a number of creatures that you must fight your way through in order to reach the end of the stage. However, just because they are there does not mean that you have to fight every one of them. Don't forget: if you have the Mantle, you can fly. This means you can fly over the small platform that are difficult to jump over, or have Hangers hanging from the bottom that shoot at you. In fact, there are two items that you can only collect by flying; a 100 Bullets and a Potion. However, the single most important time-saver is this: don't bother fighting the Go-Lem sub-boss.
When you reach the final stretch and are being attacked by Go-Lem, the best strategy is to simply ignore him. You can obtain items for beating him, but you are likely to lose more health than you stand to gain. And beating him is entirely optional, it won't prevent you from advancing to the final boss if you ignore him. Once you encounter him, run below him and continue advancing to the stairs at the end. Flying helps quite a bit as well.
Final Boss is easier than you might think
When you arrive in the final section of the stage, the background and the music will change. Konami aficionados will probably recognize this as a scene out of Contra, an arcade game that was not yet available on the Famicom, but was in development and would be published less than a month later. The first thing to know about this boss is that antibodies will appear continuously to defend it. You will have to do your best to contend with the massive onslaught of antibodies while you damage the boss. The second thing to know is that there is an incredibly easy way to position yourself to attack the boss with greater frequency than if you were to stand on the ground. With King Kong, you can actually jump on the head closest to the ground. Then you can turn around and face the middle head and attack it with a character like Mikey, using his Slingshot attack. From there, you can destroy the boss faster than the mass of antibodies can drain a character's entire health meter.
Get out fast!
As soon as the Final Boss is defeated, a timer will appear, and the gigantic organism will begin to self-destruct. You have just enough time to make it back to your space craft with barely any seconds to spare. Don't waste any time, get moving back to the start of the stage. You will not encounter any enemies on the way out, so the only thing you need to worry about are difficult jumps. However, if you rely on flying through the stage, you won't even have to worry about the jumps. Make your way back to the start of the stage as fast as you possibly can, and you should be climbing up the final staircase just as the timer is winding down. Once you reach the surface, you won't have to worry about the timer. However, if you don't make it out in time, you will have to repeat the entire stage over again. Once you succeed, you will escape from the organisms head, and you will be treated to the ending and credits. After the credits are over, the final scene is actually a back-ground music test. Push and to change the music selection, and press to start the music. Congratulations.