In Jets'n'Guns, the player starts out as a freelancer, contracted to drive out a gang of criminals from a sector of space. Soon, the player is contacted by their old commanding officer from a previous war, Col. Troubleman, who is based aboard the United Space Ship Impotence. He explains that Xoxx, the evil dictator, has appeared again and has kidnapped a scientist, Professor Von Hamburger. The professor was developing a gigantic quantum cannon, which he intended to use for peaceful purposes. Xoxx, however, wants the cannon because it could, theoretically, destroy the entire universe with a single shot. Erecta Von Hamburger, the professor's daughter, also contacts the player, but she is mainly concerned with the rescue of her father.
The player first has to steal a better fighter, the TMIG-226, from the heavily guarded FeX labs. The player then has to rendezvous with the USS Impotence, and is only just saved from destruction by pirates by a well-timed volley of torpedoes from the Impotence. The majority of the following missions involve assaults on Xoxx's forces and attempts to ascertain the locations of the professor and the quantum cannon.
Eventually, after many battles against Xoxx's forces and hench-beings, the player rescues the professor. Soon after, the location of the completed cannon, the Lord Chaos Mk 1, is discovered. However, when the player finally defeats Xoxx, Xoxx escapes in a "backup time washing machine", his parting message revealing that it is too late to stop the cannon firing. The universe is destroyed, leaving the player's ship flying in a field of rocky debris as the credits roll. Eventually, a time warp that featured earlier in the story re-appears, bringing the player back to the beginning of the game, except set on a harder mode.
Between levels, players are given the option to buy upgrades for their ship. Some of the most vital upgrades are for maneuverability, speed, and cooling. They can also give their ship a new paint job for free. Another item is the Atarix, which gives players a chance to unlock crates found when they destroy transport ships during a mission. There are several upgrades that boost the ship's defense and provide slow armor regeneration, such as shields and nanomachines. Other upgrades give players bounties for killing certain enemies, and bonuses for mass killings of enemy troops. There are also upgrades that allow players to customize up to five different weapon profiles, which can be switched mid-game, or allow players to change the angle of their weapons to adapt to changing strategic situations.
Between levels, players are given the option of buying weapons. As the game progresses, more weapons and items are made available. The fighter the player starts with only has slots for two front weapons and rather limited ship upgrades. The TMIG-226 has slots for one bombing system, one missile system, three front weapons, and one rear weapon. Some weapons can only be used in the front or rear slots. There is a large variety of weapons, ranging from flamethrowers to electro-balls to acid guns. Most weapons can be upgraded after they are bought. This may enhance power, projectile velocity, rate of fire, or the nature of the attack itself. When viewing the status of an individual weapon, meters are shown that indicate its power, heat generation and speed ratings.
Most weapons give off heat when fired, indicated by a heating gauge. This heat dissipates when firing ceases. If the needle passes the orange and then red zones of the gauge the ship overheats, and it will be unable to fire until the needle passes back behind the orange zone. This makes upgrading the cooling system essential. With an improved cooling system, the ship will take longer to overheat, and will cool down faster. Missiles and bombs do not generate heat. The rate of fire for missiles is determined by their upgrade level. Bombs are the only weapons that have a limit pertaining to how many can be fired at any given time. Each bomb that is dropped uses up a portion of a slowly replenishing 'bomb meter'; the amount used by each bomb decreases with upgrades.
Of note is the soundtrack, composed and performed by Machinae Supremacy. The band created over 50 minutes of original music for the game in a variety of styles. The band provides downloads on their site containing the game soundtrack – however the song "Hero" is available separately — in MP3 and Ogg format. These downloads are of higher quality and are slightly longer than the versions included with the game. The music included with the game has been trimmed to allow for looping, and the quality reduced to make the download size practical. The soundtrack was created completely free of charge, though the expansion tracks were paid for.
Sometimes, the Jets'n'Guns Soundtrack is credited to the game music production company Hubnester Industries. This is because Hubnester is owned by three of the members of Machinae Supremacy, using the same composers for both. One of the places where Hubnester is credited is at the web site of Hubnester Industries.