Guinea, meanwhile, narrowly beat Uganda in their opening game on Friday.
Botswana have never qualified for the World Cup in their entire history, having failed to even make it to the second stage of qualifying last time around when losing 1-0 to Malawi in the opening round.
With the upcoming World Cup in 2026 set to be expanded to 48 teams, Africa will benefit from having nine guaranteed spots in North America, with one of the group runners-up having to navigate an intercontinental playoff.
As such, there is a glimmer of hope for potential debutants such as Botswana, but their 3-2 loss at home to Mozambique on Thursday was not the start which head coach Didier Gomes Da Rosa and his players would have been hoping for.
Clearly, Botswana can not afford back-to-back home defeats if they are to stand any realistic chance of claiming one of the top two spots in Group G, making their test against Guinea on Tuesday an extremely important one.
Guinea, on the other hand, began their campaign with a victory against Uganda, although they left it late via Seydouba Cisse's 94th-minute winner.
Fahad Bayo's equaliser had looked like giving the visitors an unlikely point after Aguibou Camara's early goal, but Cisse's strike ensured that the National Elephants moved level on points with Algeria and Mozambique after the opening round of fixtures.
Unlike their forthcoming opponents, Guinea are relative regulars at the Africa Cup of Nations, having progressed to the knockout stage in six of the last 10 major tournaments in Africa; they will look to improve that record in Ivory Coast in the New Year.
However, they have never qualified for a World Cup before, meaning they will be desperate to make it two wins from two in Francistown on Tuesday in order to keep pace with group favourites Algeria.
Given that two substitutes scored against Mozambique, it would not be a surprise if former Mauritania boss Gomes opted to make some changes for this match, with Tlhalefang and Mogakolodi Ngele likely to be at the forefront of his thoughts.
Kaiser Chiefs centre-back Thatayaone Ditlhokwe should lead the hosts from the back once again, but they will need an improved defensive performance in order to claim a positive result.
Guinea, meanwhile, are without their captain Naby Keita due to injury at present; the former Liverpool midfielder has had a disrupted beginning to his time in Germany with Werder Bremen.
Serhou Guirassy is tearing it up in the Bundesliga this season with 15 goals in eight league starts for Stuttgart, but his recent hamstring issue meant that he only featured from the bench against Uganda. The 27-year-old could start on Tuesday.
Botswana possible starting lineup:
Dembe; Velaphi, Ditlhokwe, Gaolaolwe, Mangolo; Modingwane, Mohutsiwa, Ditsele, Ngele; Orebonye, Tlhalefang
Guinea possible starting lineup:
Kone; Conte, Jeanvier, Sow, Sylla; Diawara, Guilavogui; Camara, Moriba, Bayo; Guirassy
We say: Botswana 1-2 Guinea
With Guinea sitting 68 places above Botswana in FIFA's world rankings, there should only be one winner here, but Guinea made hard work of their victory against Uganda on home soil.
As such, they are unlikely to run away with things against Botswana, but we expect the visitors to just about maintain their 100% record in the end.
For data analysis of the most likely results, scorelines and more for this match please click here.