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) and his starting item Bloody Lust, is both not a very good item (being previously nerfed, making it less effective) and a special item, which decreases the chances to find other special items throughout the rest of the game. Bloody Lust can help at the beginning of the game, giving you some 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 and 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 (causing weird knockback on enemies, making you get hit often), and he has a fairly low rate of fire.
- Try to get extra Heart Containers or Soul Hearts (Dessert, Dinner, etc for regular hearts or tinted 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 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 (tears destroyed by the candle's flame also count towards added damage).
- Visiting Curse Rooms is not recommended early on, unless you're sure you can replenish your health.
- Due to starting with 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.
- Bloody Lust (of course)
- Health increasing items (Dinner, Stem Cells, Breakfast, etc.)
- Prayer Card
- Book of Shadows
- The Wafer
- The Parasite
- Spoon Bender (Although less effective for Samson due to his high shot speed)
- The Halo
- Growth Hormones
- The Nail
- Book of Revelations
- Halo of Flies
- Super Bandage
- Little C.H.A.D. (Mediocre, causes Relic to drop less often)
- The Relic
- The Candle
- Magic Mushroom
- Tear increasing items (such as Mom's Eye, The Sad Onion, Wire Coat Hanger, etc.)
- Mutant Spider
- XIII-Death tarot card
- 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
- Guppy's Head (Blue flies will clear a few enemies at the start of each room, causing Bloody Lust to activate immediately)
- Kamikaze! (Can be good if walking into walls, which makes you not take damage)
- Razor Blade
- Blood Rights
- IV Bag (Alright if there are spare hearts just laying around)
- Dead Bird (Is not so much "bad" as you shouldn't activate it too often ideally, because you don't want to take damage)
- 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, unless you have gotten to a decent range stat through pills or items)