By his low starting stats, a run played as Samson could be difficult to finish (low range and tears, low-average speed and attack power) but his starting item Bloody Lust, is a pretty good item (in spite of the nerf it suffered, making it less effective) which helps at the beginning of the game, gives you power to take down foes. However, his starting health is very low (one Heart Container and one Soul Heart), making him a very fragile character. He is described by Edmund McMillen as the "Berserker"; he needs to survive to deal a very high amount of damage.
Samson is a tough character to use in that he has generally low stats all around starting out. He has to rely a lot on his Bloody Lust item, which is not always helpful. Rooms containing fewer enemies create a bigger challenge for him, as he is not able to use the power boost from Bloody Lust to his advantage. This becomes an even bigger challenge when he has to face bosses that don't spawn weaker enemies (Monstro, The Carrion Queen, Peep, etc.) and don't have sections that can be destroyed (like Larry Jr. and The Hollow). His shot speed is very quick, but this advantage is worsened by his very slow rate of fire.
- Try to get extra Heart Containers or Soul Hearts (Dessert, Dinner, etc for regular hearts or X Marks the Spot rocks and Shops for Soul Hearts) as often as possible. You must boost his defense to grant him a chance to survive.
- When entering a room full of enemies, try to pick on the weakest foe first. Each successive kill will make help you clear the room faster, thus helping you conserve precious health.
- In the case of fighting a boss who summons monsters (Widow, Chub, Gurdy, some Horsemen, etc), you should kill some of them before defeating the boss; the Bloody Lust gives you attack power each time a foe is killed, then you will be more powerful against the boss.
- As he starts with no bombs/keys or even money, think before you use one of them; they are precious, especially if you can find a Secret Room. It can contain very useful items or money to buy boosts at the shop.
- Like Judas, avoid doing deals with the devil too early in the game. Samson's base health is too low to risk such a lack of life.
- Items like The Candle help you deal damage until Bloody Lust gives you more attack power.
- Visiting Curse Rooms is not recommended early on, unless you're sure you can replenish your health.
- Because of his starting item, the Bloody Lust, he can do fairly well in the Challenge Rooms. Boss Challenge Rooms are also a possibility.
- Try to find Trinkets that give you more bombs/keys, like the Flat Penny and the Burnt Penny. Isaac's Fork is good too if you are getting hit often.
- Attack flies are very helpful, as they can deal enough damage to kill weaker enemies and build damage via Bloody Lust.
- Bloody Lust (of course)
- Health increasing items (Dinner, Stem Cells, Breakfast, etc.)
- Prayer Card
- Book of Shadows
- The Wafer
- The Parasite
- Spoon Bender
- The Halo
- Growth Hormones
- The Nail
- Book of Revelations
- Halo of Flies
- Super Bandage
- Little C.H.A.D.
- The Relic
- The Candle
- Magic Mushroom
- Tear increasing items (such as Mom's Eye, The Sad Onion, Wire Coat Hanger, etc.)
- The Necronomicon and Spider Butt
- Charm Of The Vampire
- Lucky Foot
- The Common Cold
- Flight granting items (Lord of the Pit, Holy Grail, Trandscendence, etc.)
- Range increasing items (Mom's Lipstick, Mom's Heels, Mini Mushroom, etc.)
- A Lump of Coal
- Mom's Contacts
- Spectral tear granting items (Ouija Board, Dead Dove, Spirit of the Night, etc.)
- Guppy's Paw
- Razor Blade
- Blood Rights
- IV Bag
- Dead Bird
- Chocolate Milk (Charged shots are weaker with Bloody Lust)
- Number One (Samson's range is too poor to take advantage of the maxed tears without being able to survive comfortably)