The story focuses on a group of students at a high school and the various romantic attachments that the characters feel for each another.

Tsuyokiss originally began as an eroge for Windows by video game developer Candy Soft first released on August 26, 2005.

Later, a senior female student, Otome Kurogane, knocks out several of the main characters one day when they are trying to sneak into school after being late.

Suddenly, Otome decides to move into the same house as Leo, whose mediocre life is changing into something a bit more exciting.

The anime version's plot of Tsuyokiss differs from that of the video game's in that Sunao Konoe is the main protagonist of the story.

Sunao Konoe (近衛素奈緒, Konoe Sunao) Leo Tsushima (対馬レオ, Tsushima Reo) Nagomi Yashi (椰子なごみ, Yashi Nagomi) Shizuka Asada (浅田静香, Asada Shizuka) Noriko Nishizaki (西崎紀子, Nishizaki Noriko) Youhei Murata (村田洋平, Murata Youhei) Erika Kiriya (霧夜エリカ, Kiriya Erika) Yoshimi Satou (佐藤良美, Satō Yoshimi) Kinu Kanisawa (蟹沢きぬ, Kanisawa Kinu) Shinichi Samesuga (鮫氷新一, Samesuga Shinichi) Subaru Date (伊達スバル, Date Subaru) Otome Kurogane (鉄乙女, Kurogane Otome) Inori Ōeyama (大江山祈, Ōeyama Inori) Heizou Tachibana (橘平蔵, Tachibana Heizou) Honoka Konoe (近衛ほのか, Konoe Honoka) Tsuchinaga (土永) Tsuyokiss's first appearance was in the form of a visual novel video game for the PC developed by Candy Soft and released on August 26, 2005.

Its scenario was written by NOB because Takahiro, who is a director and a scriptwriter of Tsuyokiss, left Candy Soft.

A soundtrack and Character image song album named Tsuyokiss ~Cool×Sweet~ Complete Selection based on the anime version was released by SOL BLADE/Tree Fat Samurai.

The original Tsuyokiss game was voted the 14th most interesting galge ever by readers of Dengeki G's Magazine in an August 2007 survey.